EP1677809A1 - Banque de cellules pour transplantation de leucocytes autologue en cas besoin - Google Patents

Banque de cellules pour transplantation de leucocytes autologue en cas besoin

Info

Publication number
EP1677809A1
EP1677809A1 EP04768677A EP04768677A EP1677809A1 EP 1677809 A1 EP1677809 A1 EP 1677809A1 EP 04768677 A EP04768677 A EP 04768677A EP 04768677 A EP04768677 A EP 04768677A EP 1677809 A1 EP1677809 A1 EP 1677809A1
Authority
EP
European Patent Office
Prior art keywords
leukocyte
leukocytes
blood
donor
individual
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP04768677A
Other languages
German (de)
English (en)
Inventor
William Arthur Spiers
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lifeforce Immune System Bank PLC
Original Assignee
Lifeforce Immune System Bank PLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lifeforce Immune System Bank PLC filed Critical Lifeforce Immune System Bank PLC
Priority to EP09011764A priority Critical patent/EP2133087A3/fr
Publication of EP1677809A1 publication Critical patent/EP1677809A1/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02—Blood transfusion apparatus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/02—Blood transfusion apparatus
    • A61M1/0272—Apparatus for treatment of blood or blood constituents prior to or for conservation, e.g. freezing, drying or centrifuging
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00—ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • G16H10/60—ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/40—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture

Definitions

  • the invention relates to a process for producing a leukocyte bank, to leukocyte cell banks and preserved leukocyte compositions created thereby and to various forms of therapy based thereon
  • CAT Contingent autologous transplantation
  • a form of therapy has recently been described (see WO 00/29551 and WO 01/88099) in which various tissues (including leukocytes) are removed from a healthy donor and stored in a tissue or cell bank for later autologous transplantation in the event that a need for such autotransplantation arises at some future date
  • This form of therapy is herein referred to as contingent autologous transplantation (CAT) therapy
  • CAT contingent autologous transplantation
  • CAT contingent autologous transplantation
  • the need for CAT therapy is likely to arise in only a fraction of the healthy population
  • the effectiveness of CAT therapy depends crucially on the generation of comprehensive cell and tissue banks in which deposits from a large percentage of the population are included
  • CAT therapy be facilitated by the construction of comprehensive tissue banks
  • tissue banks the nature of CAT therapy places unique and stringent demands on any such tissue bank
  • CAT therapy implies a large number of participating donors (and consequently a large number of deposits), relatively long-term storage, good retention of tissue function over time and great flexibility in ultimate therapeutic use
  • cent ⁇ fugation Centnfugation e g at about 3900 rpm partitions the various components of the whole blood into three distinct layers a blood plasma layer (of relatively low density), and red blood cell layer (of relatively high density) and a layer of intermediate density consisting predominantly of leukocytes and thrombocytes (platelets) This latter layer normally appears at the interface between an upper plasma and lower red blood cell layer after centrifugal separation, and is known as the buffy coat
  • red blood cell fraction is usually stored chilled for up to 35 days, and can be used for treating anaemic patients, victims of trauma and patients undergoing surgery
  • the plasma is generally frozen below -30°C for up to one year, and can be used to reverse anticoagulant treatment and as a component in massive transfusions
  • the thrombocytes stored at 20°C and continually agitated to prevent clotting, can be used to prevent bleeding in leukaemic patients or those undergoing chemotherapy or massive blood transfusions
  • the leukocytes present in the buffy coat fraction are usually regarded as an unwanted contaminant, since they can induce profound and possibly dangerous immunological changes if transfused inappropriately For this reason, steps are usually taken to limit the collection of these cells during blood sampling (e g by the use of in- line filters during blood donation)
  • Such apparatus known to those skilled in the art as a Wood (pack or bag) press, usually features one or more vertical press plates between which the bag can be introduced and which act to drive the different layers successively out of the pack when one plate is advanced towards the other This usually results in the plasma layer being expressed first, followed by the buffy-coat The red blood cell fraction can then be expressed last, or retained as a residual fraction in the pack
  • the bag press can be designed to express the plasma and red blood cell layers from opposite ends of the pack simultaneously, leaving the buffy-coat as a residual fraction
  • Leukapheresis is a specific form of apheresis which involves the selective separation and removal of leucocytes from withdrawn blood, the remainder of the blood then being retransfused into the donor During leukapheresis, the removed blood is passed through a cell separation device which separates nucleated white blood cells from red blood cells and plasma outside the body The red blood cells and plasma are returned to the individual, as part of the separation process The process is continuous with blood being removed and returned almost simultaneously after various extractions have been performed Leukapheresis therefore makes it possible to remove and return the entire blood volume of the individual several times over and separate out and keep large numbers of white cells without detriment to the individual The technique therefore relies on the establishment of a vein-to-vein extracorporeal blood circulation and extraction of leukocytes from the recirculating blood
  • Leukaphereses are generally automated, and conducted using either continuous or interrupted flow centnfugation or filtration techniques, as described in "Leukapheresis and Granulocyte Transfusions", published by American Association of Blood Banks, Washington DC (1975)
  • Cobe 2997 (Cobe BCT, Lakewood, CO), the Cobe Spectra, the Cobe 2991 , and the Haemonetics V50 (Haemonetics Corp , Braintree, MA) Any of these systems can be used in the processes of the invention, but preferred is the Cobe® system (Cobe BCT, Lakewood, CO, USA), which is capable of extracting between 40% and 50% of the total white cells in the whole blood that passes through the separator, and which can achieve a flow rate of 40-60 ml or more per minute
  • the present inventors have found that a combination of (a) deposit redundancy, (b) stringent control over cryogenic preservation parameters through the use of separate holding and storage vessels, (c) the use of closed (or functionally closed) blood processing apparatus, (d) digital storage of information, and (e) double containment vessels for cell storage is essential for fulfilling the unique demands made on a leukocyte bank intended to support CAT therapy
  • the present invention provides a process for producing a leukocyte bank suitable for CAT therapy comprising the steps of
  • the holding vessel serves to hold the leukocytes during the isolation and collection steps (which may take several minutes or even hours to complete) and permits stringent control over the mixing and preserving steps
  • the use of a separate holding vessel permits control over the incubation time and concentration of the leukocytes in the cryogenic preservation medium prior to freezing
  • the size of a leukocyte bank (in terms of the number of deposits) necessary to serve as the basis for broadly applicable CAT therapy is so large that the chance of proximal barrier failure p, although small at the level of individual deposit, becomes critical to the integrity of the bank as a whole This is because in cases where the bank size (the number of filled storage vessels n) approaches or exceeds 1/p, proximal barrier failure in any one storage vessel becomes inevitable over the lifetime of the bank Since the cell bank must serve as a resource for CAT therapy, the use of uncontaminated, autologous leukocytes is critical such an event could therefore compromise the integrity (and usefulness) of the entire bank
  • double containment is a term of art defining a container having at least two barriers a proximal barrier, in contact with the separated leukocytes, which contains the leukocyte sample and isolates it from the outside environment, and a secondary barrier which acts as a fail-safe to isolate the leukocyte sample from the outside environment in circumstances where the proximal barrier fails (for example after accidental physical or chemical trauma)
  • independent as applied to the storage vessels of the invention, is intended to define vessels which can be independently stored (as defined herein)
  • the independent storage vessels of the invention may have non-contiguous internal volumes, may not share a barrier and may be entirely separate (or separable) vessels
  • the storage vessels of the invention contain, or are in fluid communication with, a cryopreservation medium
  • the cryopreservation medium is simply present in liquid form within the storage vessel
  • the cryopreservation medium may be isolated from the holding vessel(s) by any convenient means, for example by (a) a valve, (b) a breakable seal, (c) gravity in conjunction with the spatial arrangement of the holding and storage vessels, and/or (d) surface tension within a tube connecting the holding and storage vessels
  • the cryopreservation medium is in fluid communication with the storage vessel but not contained therein, for example being held in a satellite cryogenic medium vessel
  • the satellite cryogenic medium vessel may be reversibly isolated from the storage vessel by any convenient means, for example by (a) a valve, (b) a breakable seal, (c) gravity in conjunction with the spatial arrangement of the satellite and storage vessels, and/or (d) surface tension within a tube connecting the satellite and storage vessels
  • two or more aliquots are used according to the invention in order to provide for deposit redundancy
  • three, four, five or greater than five separate aliquots are used according to the invention
  • the storage vessels are preferably detachable from the holding vessel and from any ancillary tubing and/or satellite vessels, for example by releasable clamps, releasable docking components, tearable seals, heat crimping or by use of so-called "docking systems" for sterile sealing
  • the independent storage systems into which the aliquots are retnevably deposited are independent in the sense that they do not share a determinant of viability selected from (a) power supply and/or (b) site or location For example, in cases where the storage systems depend on a supply of electricity for their continued cryopreservation, then the electricity supplies must not originate from a single generator or supplier
  • each independent storage system is sited to be geographically remote from its counterpart(s), so lessening the chances of coincidental destruction or damage by natural or man-made disasters (such as fire, flood or contamination)
  • closed system in the context of the process of the invention, is used to define blood processing apparatus consisting of elements which are sterile and isolated from the outside environment by aseptic bar ⁇ er(s) and in which all components are fully integral, being attached and/or assembled at the manufacturing site
  • the term functionally closed system in the context of the process of the invention, is used to define blood processing apparatus consisting of elements (e g tubing sets) which are assembled at the device manufacturing site and which use sterile barrier filters (e g 0 22 micron filters) or so-called "docking systems" for the sterile interconnection by the end user to generate a wide variety of arrays of tubing, channels, filters, satellite bags and other vessels
  • the cryogenic preservation step (f) conveniently comprises freezing to a temperature at or below about -160°C, which can be achieved using liquid nitrogen If longer periods of storage and/or enhanced retention of functionality are required then freezing to a temperature at or below about -269°C may be effected using liquid helium
  • cryopreservation media Any of a wide range of suitable cryopreservation media may be used according to the invention, but preferred are media comprising a suitable penetrating cryoprotectant Particularly suitable for use as a penetrating cryoprotectant is DMSO, which may be used for example at a concentration of up to 10%
  • the cryopreservation medium may further comprise an anticoagulant (such as acid citrate dextrose, EDTA, hepa ⁇ n or mixtures thereof), a nuclease (for example a Dnase and/or Rnase as well as a physiologically acceptable medium (for example, phosphate buffered saline)
  • the cryopreservation medium may also further comprise a protemaceous composition, such as blood serum or a blood serum component and/or a sugar and/or a polysacchande (which may be particularly preferred in embodiments where plunge freezing is employed)
  • compositions for use in the cryogenic preservation media of the invention comprise blood albumin (e g bovine serum albumin or human serum albumin)
  • blood albumin e g bovine serum albumin or human serum albumin
  • human blood serum isolated from the blood sample of the donor individual This can be isolated as a co- product together with the leukocytes
  • any donor may be used as a source of blood sample in the processes of the invention, provided that the donor is healthy, as herein defined
  • the invention finds particular application in relation to donor individuals which are predisposed to a leukocyte deficiency, are not in remission from a leukocyte deficiency, are juvenile, adolescent or adult, are at risk of developing a leukocyte deficiency, are human individuals between the ages of about 12 to 30 (e g 15 to 25) and/or have a fully-developed immune system
  • the blood sample for use in the process of the invention may be one which is in fluid communication with the donor individual (for example, in circumstances where leukapheresis is used to selectively separate the leukocytes)
  • the sample is an isolated blood sample (as defined herein)
  • the leukocytes separated in step (b) may comprise (or consist essentially of) granulocytes, lymphocytes and/or monocytes. In many embodiments of the invention, no steps are taken to enrich for (or isolate) any particular class (or classes), subpopulations or cell types
  • the separation step (b) comprises the selective separation of a particular class or type of leukocyte This may be done in circumstances where it is desired to effect the selective separation of B-cells and/or T-cells and/or dendritic cells (or mixtures thereof)
  • the information stored in step (i) comprises at least that necessary to permit matching of deposit with donor, in order that later autologous transplantation can be carried out
  • the information comprises genetic information, the date at which the blood sample was collected from the donor individual, the age and sex of the donor individual, the clinical status of the donor individual, the medical history of the donor individual, biographical data identifying the donor individual, details of the processing and storage conditions used to prepare the deposit as well as data identifying the person(s) responsible for processing the sample(s)
  • genetic information preferably comprises sequence information relating to one or more gene(s), single nucleotide polymorphism (SNP) data and/or one or more genetic fingerp ⁇ nt(s)
  • Any suitable digital information unit may be used to store the information
  • this takes the form of at least one digital computer comprising a database
  • the database may carry data on a carrier of any convenient form
  • the information is stored independently on two or more carriers so that the database exhibits redundancy This protects against data loss in the event of failure, corruption or loss of one of the computers or data carriers
  • the process further comprises the step of labelling the storage vessels of step (f) with information sufficient to permit matching of the leukocyte deposit and donor
  • the storage vessels may be labelled with information (a) describing the contents of the vessel (for example, sample size, number and/or volume), and/or (b) identifying the leukocyte bank, and/or (c) recording the date at which the blood sample was collected from the donor individual, and/or (d) comprising a statement that each package is for single patient use only, and/or (e) comprising instructions for opening, aseptic presentation and further storage
  • the labelling may comprise the physical attachment of an information carrier (e g a bar code) to the storage vessels themselves
  • the labelling may be effected by the non-physical association of the vessels with the information carrier (for example, via the correlation between the physical geometry or organization of the deposits in the bank and the entries in the database)
  • the invention also contemplates treatment of the leukocytes, for example including any or all of the following in vivo prior to provision of the blood sample, in vitro prior to separation step (b), in vitro after separation step (b) but prior to preservation step (f) and/or in vitro after preservation step (f)
  • the leukocytes are selectively separated in step (b) using leukapheresis apparatus (as described in more detail herein)
  • the leukapheresis apparatus preferably comprises (a) a separation device (e g a centrifuge rotor or filter), (b) a leukapheresis tubing set, and (c) one or more pumps for conveying the sample through the tubing set and the separated leukocytes into the collection vessels
  • a separation device e g a centrifuge rotor or filter
  • a leukapheresis tubing set e.g a centrifuge rotor or filter
  • one or more pumps for conveying the sample through the tubing set and the separated leukocytes into the collection vessels
  • Non-automated or manual techniques may also be used to separate and/or collect the leukocytes in steps (b) and (c) of the process of the invention
  • batch centrifugal separation and collection e g by bag pressing
  • gravity leukapheresis as described in US 4111199
  • the invention contemplates a process for producing a leukocyte composition for autotransplantation into a donor individual comprising the steps of (a) producing a leukocyte cell bank by the process of the invention, (b) matching the donor individual with a leukocyte deposit to identify an autologous leukocyte deposit using the information stored in step (h), (c) retrieving a storage vessel containing an aliquot of preserved autologous leukocytes, (d) revitalizing the preserved autologous leukocytes to produce a leukocyte composition for autotransplantation into the donor individual
  • the invention also contemplates a leukocyte composition and a leukocyte cell bank obtainable (or obtained) by the process of the invention
  • the invention contemplates the leukocyte composition of the invention for use in therapy, for example in CAT therapy
  • leukapheresis is a term of art used herein to define a procedure involving the selective separation and removal of leukocytes from the withdrawn blood of a donor, the remainder of the blood then being retransfused into the donor
  • a leukapheresis device is a term of art defining any device capable of performing leukapheresis, irrespective of the means employed in the device to separate and remove the leukocytes
  • isolated leukapheresis is used herein to define a novel form of leukapheresis which is performed on an isolated blood sample
  • isolated blood sample is used herein to define a blood sample which is not in fluid communication with the blood of the donor from which it originated.
  • the leukapheresis device is not in fluid communication with the individual providing the blood sample and/or the remainder of the blood in the sample is not retransfused into the individual
  • autotransplantation is used herein to define autologous transplantation (autogeneic or self-to-self transplantation), wherein the term autologous is used to indicate that the transplantation is to the same organism (i e the same individual) from which the cellular material (e g leukocytes) was removed
  • transplantation defines any procedure involving the introduction of cellular material (e g leukocytes) into an organism, and so any form of transplantation or grafting known in the art is encompassed
  • dormancy is used herein to define any state of suspended animation or stasis, and procedures for achieving this are well known in the art, as described below Any of the known procedures may be used, including cryopreservation
  • the leukocytes may be held or maintained in a quiescent, inactive or non- proliferating state
  • healthy is used herein in relation to an individual donor to indicate that the individual is not suffering from a leukocytic deficiency (as herein defined)
  • the term healthy as used herein encompasses non- diseased individual donors in a state in which the individual donor is not suffering from any disease or disorder, or is not manifesting any symptoms of said disease or disorder (i e is asymptomatic or is in a pre-clinical condition)
  • term healthy as used herein encompasses individual donors not suffering from, or demonstrating symptoms of, the disease or disorder which it is subsequently intended to treat by the autotransplantation procedure II Blood samples
  • the invention may be applied to any form of blood sample, provided that the sample comprises at least some leukocytes from the individual donor
  • the blood sample may be subjected to various treatments ex vivo prior to use in the process of the invention Typically, for example, the blood sample is chilled prior to use Other treatments may include the addition of preservatives and/or anticoagulants
  • the blood sample may also be treated in vivo prior to collection by administering various agents to the donor individual before or during sample collection Examples of treatments (which may be applied ex vivo and/or in vivo) are discussed in more detail in the section entitled "Leukocyte treatments", below
  • a number of samples e g several 450-500 ml samples
  • a period of time e g over 2-3 weeks, preferably 2-3 months or over 6 months or a year, 2 or 3 years or more
  • One or more of these can then be divided or combined into a number of leukocyte cell bank deposits
  • the removal of a unit of blood is commonplace with over three million units of blood being taken, for allografting, from individuals annually in the UK alone
  • Restorative autotransplantation is a form of therapy that might ultimately be indicated for any individual Consequently, the invention may be usefully applied to the generation of comprehensive leukocyte cell banks covering as large a number of different individuals as possible in order that restorative autotransplantation can be carried out in any of the represented individuals should the need arise
  • the invention be applied as broadly as possible so that a comprehensive leukocyte cell bank can be assembled
  • the quality of the individual deposits will depend (at least to some extent) on the health status of the individual donor at the time of blood sample donation, it is preferred that the blood sample for use in the processes of the invention be taken from healthy individual donors
  • the blood sample for use in the processes of the invention may advantageously be obtained from individual donors when they are young, preferably in adolescence or early adulthood
  • blood sampling preferably multiple sampling
  • sampling is from the age of 16 or 17 upwards, for example in the age range 16 to 30, 17 to 30, or 18 to 30, or perhaps 18 to 35 or 40
  • the cells be obtained when the host organism is mature, or reaching maturity, but before the processes of ageing or senescence have significantly set in
  • cells may be obtained at any postnatal life stage e g from juvenile host organisms e g in mid-to late childhood, or even infants, or from older individuals
  • Sampling from post-natal or older hosts allows multiple samples to be collected, thereby increasing the opportunity of storing sufficient number of cells
  • sampling from juvenile or older hosts overcomes the ethical requirements such as providing informed consent
  • sampled cells from blood in particular, will contain a greater proportion of valuable mature T-cells capable of recognising aberrant cell populations, such as cancer cells or virally infected cells
  • a mature immune system i e not foetal or neonatal
  • the invention contemplates the use of blood samples collected from donor individuals at a stage when there is no direct prediction, suggestion, or suspicion that a particular disorder or disease may develop, for use against a future possible or unpredicted event, or an event which may occur simply by chance, rather than an anticipated or suspected or predicted illness or condition
  • the donor individual is not predisposed to, or at risk from, any particular disease or disorder e g not exhibiting any symptoms or manifestations predictive of a subsequent disease or disorder
  • the host organism is preferably not suffering from any injuries or damage which may give rise to an anticipated or expected condition
  • the blood sample for use in the invention be obtained from the donor individual before any disease or disorder develops or manifests itself, and more preferably when the host organism is in general good health, and preferably not immunocompromised in any way
  • leukocyte deficiencies which term is used herein to indicate a condition in which the administration of autologous leukocytes is indicated Such conditions therefore include those in which an individual has acquired a disease, infection or condition involving leukocyte dysfunction or a disease, infection or condition in which the augmentation or stimulation of endogenous leukocyte activity is indicated Detailed examples of particular leukocyte deficiencies are set out in the section entitled "Exemplary indications", below
  • an offending cell e g a virally infected or tumour cell
  • an offending cell e g a virally infected or tumour cell
  • danger signals such as GM-CSF and/or TNF-alpha
  • APC antigen presenting cells
  • CTL cytotoxic T-lymphocyte
  • tumour cells do not automatically co-present danger and/or co-stimulatory signals Hence, the spawning of a tumour may lead to eradication of the very T cell clones that provide cell-mediated immunity against the tumour
  • the relevant T-cell population could now be returned to the patient, after the necessary co-stimulation of the T-cells, so as to alleviate disease
  • Co-stimulation may be provided at the same time as the cells are returned to the patient, or after they are returned through further treatment (s) of the patient, or without stimulation other than that naturally produced by the patient
  • Activation/stimulation of the cells may also initially be induced in vitro prior to reinfusion
  • the present invention therefore finds particular application in the case of individuals predisposed to the development of a leukocyte deficiency It therefore represents a means for removing leukocytes from a healthy donor individual for subsequent transplantation to that same individual in a subsequent autologous (autogeneic) transplantation procedure, when the need or desire to do so arises
  • the predisposed individual may never receive the cells because no disease to be treated by this method ever occurs, the invention nevertheless may be used to provide some form of insurance against the heightened risk of a leukocyte deficiency arising in the individual
  • individuals with no diagnosed predisposition may choose to provide samples for incorporation into the leukocyte cell bank of the invention for prospective use by themselves prior to travelling abroad Such use might include for the treatment of infections contracted whilst abroad
  • Such an approach could be used more broadly to provide for a method of augmenting the patient's immune system after surgery in order to lessen the likelihood of post-operative complications caused by opportunistic infections
  • the invention therefore, could be used as a prophylactic therapy, e g for elderly patients when they are more susceptible to disease
  • the separation and/or removal of leukocytes from the blood sample during leukapheresis need not be absolute Rather, the removal and/or separation of a fraction of the total leukocytes present in the sample is sufficient in most circumstances Those skilled in the art will readily be able to determine the appropriate size of the fraction to be removed, which will vary inter alia according to the use to which the isolated leukocytes are to be put, the size of the sample, the status of the donor, the nature of the leukocytes and the particular leukapheresis device employed
  • the leukocytes collected in the processes of the invention are to some degree isolated from the original blood sample
  • the term isolated is used here to indicate that the isolated leukocytes exist in a physical milieu distinct from that in which they occur in vivo and does not imply any particular degree of purity Indeed, the absolute level of purity is not critical, and those skilled in the art can readily determine appropriate levels of purity according to the use to which the leukocytes are to be put
  • the separation and collection of the leukocytes in the processes of the invention also does not necessarily imply that any particular class or type of leukocyte is preferentially separated and collected Rather, the leukocytes of the invention include any white blood cell, including granulocytes, lymphocytes and monocytes
  • Granulocytes include myelocytes, basophils, eosinophils and neutrophils
  • Lymphocytes include B, T lymphocytes and natural killer cells
  • Monocytes include mononuclear phagocytes and other macrophages
  • the leukocytes which are separated and collected preferably comprise one or more specific leukocyte cell types
  • a preferred cell type is the lymphocyte, especially a T-lymphocyte (T-cell) Mature T-lymphocytes are particularly preferred
  • a 100 ml sample of blood typically contains 1-2 5 x 10 8 mature T-cells and this is generally sufficient to provide an adequate representation of the entire mature human T-cell population for the beneficial effect
  • preferably at least 100 ml, 115 ml, 200 ml or 300 ml and even more preferably in excess of 400 or 500 ml of blood sample is used in order to obtain the appropriate number of mature T-cells to support a beneficial therapeutic effect for return to the individual if and when they become ill
  • Standard techniques are known in the art which permit selection of particular subpopulations of lymphocytes from a sample comprising a mixed population of lymphocytes
  • Examples of such subpopulations are CD3 ⁇ CD8 ⁇ CD4 + and CD16/56 + (natural killer) T cells and CD19 + B cells
  • any one or any mixture or combination of such subpopulations of T cells can be used in the methods, uses and compositions of the invention, and they are readily obtained by means of well known methods such as FACS (Fluorescence Activated Cell Sorting) and haemocytometry systems
  • the leukocytes may be subjected to various treatments Such treatments may, for example, result in expansion of some or all of the representative cell subsets, improve the long-term viability of the leukocytes during the dormancy period, improve their therapeutic potency and/or render their subsequent use in autotransplantation safer
  • the treatments can be carried out before or after the leukocytes are rendered dormant (and before or after autotransplantation is carried out) Moreover, the treatments may be applied after the blood sample is taken (i e be carried out ex vivo) either prior to rendering the cells dormant or after revitahzation
  • treatment of the leukocytes may be effected by co administration of a separate composition, sequentially or simultaneously with the leukocyte composition, during autotransplantation
  • Treatment of the leukocytes can be effected immediately prior to autotransplantation
  • the treatments may be applied to the leukocytes while still in vivo prior to blood sampling by the administration of e g growth factors or cytokines (see below)
  • Exemplary pre-transplantation treatments may include various genetic modifications, such as the incorporation of a negative selection marker (as described, for example, in W096/14401 , the content of which is incorporated herein by reference) Such treatment permits ablation of the leukocytes after transplantation or titration of dose versus response
  • Other genetic interventions may include regulating or modifying the expression of one or more genes (e g increasing or decreasing gene expression), inactivating one or more genes, gene replacement and/or the expression of one or more heterologous genes)
  • Other genetic modifications include the targeting of particular T-cells (as described in W096/15238, the content of which is incorporated herein by reference), and the modification of the T-cell receptor repertoire/expression with antibodies to make T-cell chimaeras
  • Treatments contemplated by the invention include the exposure of the leukocytes with one or more stimulatory molecules, for example antigens (e g cancer or viral antigens), antibodies, T cell recognition epitopes, peptides, blood factors, hormones, growth factors or cytokines or combinations thereof
  • stimulatory molecules for example antigens (e g cancer or viral antigens), antibodies, T cell recognition epitopes, peptides, blood factors, hormones, growth factors or cytokines or combinations thereof
  • the leukocytes may be treated in vitro (or in vivo prior to blood sampling) with antigens (for example cancer (e g prostate-specific antigen 1 or prostate-specific antigen 2, her-2/new, MAGE-1 , p53, Haras and c-myc) or viral antigens), antibodies, T cell recognition epitopes, peptides, blood factors, hormones, growth factors or cytokines or combinations thereof
  • antigens for example cancer (e g prostate-specific antigen 1 or prostate-specific antigen 2, her-2/new, MAGE-1 , p53, Haras and c-myc) or viral antigens), antibodies, T cell recognition epitopes, peptides, blood factors, hormones, growth factors or cytokines or combinations thereof
  • the stimulatory molecules may be synthetic, recombinant or may be purified or isolated from the human or animal body Particularly useful in this respect are stimulatory molecules selected from IFN-alpha, IFN-beta, IFN-gamma,
  • Other pre-transplantation treatments include culture of the leukocytes (or a sub-population thereof)
  • the leukocytes may be cultured to increase cell numbers
  • the cells may be passaged, according to methods well known in the art Such cultunng may be carried out before or after the leukocytes are rendered dormant, or both before and after dormancy is induced
  • the T-cells may be co-stimulated prior to transplantation and/or exposed to tumour antigens (optionally together with co-stimulatory factors) prior to autotransplantation
  • Such devices usually comprise at least three separate elements (1) a separation device (e g comprising a membrane or centrifuge rotor, which provides the forces for separating the leukocytes from the various other blood components, (2) one or more pumps for conveying the blood sample to the separation device, for removing the separated leukocytes and for maintaining the forces necessary for transfusion and retransfusion, and (3) a (normally disposable) tubing set which holds the blood and its various fractions in a particular geometry within the separation device, defines fixed channels through which the blood flows (normally in a circuit from the donor, through the leukapheresis device and back to the donor) as well as vessels (usually bags) for the collection of the separated leukocytes and/or other blood fractions or fluids
  • a separation device e g comprising a membrane or centrifuge rotor, which provides the forces for separating the leukocytes from the various other blood components
  • one or more pumps for conveying the blood sample to the separation device, for removing the separated leukocytes and for maintaining
  • leukapheresis devices Any of a wide variety of commercially available leukapheresis devices may be used according to the present invention
  • the particular way in which the leukapheresis device is operated will depend on a number of factors, including the nature of the separation device (e g centrifuge, filter etc ), the type of leukocyte sample required, the volume of the blood sample to be processed, the identity and status of the donor individual, the ultimate use to which the leukocyte composition is to be put and the nature of any treatments applied to the blood sample prior to processing according to the invention
  • the separation device e g centrifuge, filter etc
  • an automated leukapheresis device is selected to minimize the need for operator intervention and/or training
  • Commercially available leukapheresis systems vary in the time and/or expertise required of an individual to prepare and operate it For instance, reducing the time required by the operator to load and unload the tube set, as well as the complexity of these actions, can increase productivity and/or reduce the potential for operator error Moreover, reducing the dependency of the system on the operator may lead to reductions in operator errors and/or to reductions in the credentials desired/required for the operators of these systems
  • Performance-related factors are also relevant, and may be judged inter alia in terms of the "collection efficiency" of the leukapheresis system
  • the "collection efficiency" of a system may of course be gauged in a variety of ways, such as by the size of the fraction of leukocytes collected in relation to the total leukocytes present in the sample Performance may also be evaluated based upon the effect which the leukapheresis procedure has on the various blood component types For instance, it is desirable to minimize the adverse effects on at least the leukocytes of the apheresis procedure It may also be desirable to reduce platelet activation, in order to avoid degeneration in sample quality during processing
  • Cobe® system (Cobe BCT, Lakewood, CO, USA) VII Cryogenic preservation
  • the cells are frozen preferably to a temperature below - 160°C
  • a particularly preferred means of achieving dormancy is to freeze the cells to the boiling point of helium (He), i e to about -269°C or below
  • the cells may be suspended in a suitable medium (e g containing up to 10% DMSO) and cooled at a controlled rate (e g 1°C per minute to -70°C, then into liquid/gas N 2 )
  • a suitable medium e g containing up to 10% DMSO
  • a controlled rate e g 1°C per minute to -70°C, then into liquid/gas N 2
  • Such conventional procedures may be adapted to cool the cells into He/N 2 mixtures or He Alternative methods of achieving and/or maintaining cell dormancy include cooling to 4°C VIII Revitalization
  • the cells are revitalised prior to use in transplantation Again, this may be achieved in any convenient manner known in the art, and any method of revitalising or reviving the cells may be used
  • this may, for example be achieved by thawing and/or diluting the cells
  • Techniques for revitalisation are well known in the art Cells may be thawed by gentle agitation of the container holding the cells in water at 37°C, followed by dilution of DMSO to 1% or below, e g with medium or serum
  • Cells may be implanted immediately or after recovery in culture Revitalisation is designed to re-establish the usefulness of the cells e g in prophylaxis or curative therapy
  • the leukocyte compositions of the invention are banked, thereby creating a leukocyte bank Any suitable cell banking system may be employed, provided that the deposits are retrievable for autotransplantation This implies the use of some form of labelling, but this need not be in the form of a physical appendage to the individual deposits
  • the leukocyte cell bank of the invention may comprise a plurality of cell storage units for storage of leukocyte compositions
  • the cell banks of the invention may further include a digital information unit for digitally storing information relating to the identity, location and medical history of the donor individual and/or the conditions associated with the particular deposit (for example relating to the date at which the blood sample was collected from the donor individual, the processing conditions and details of any treatments applied to the leucocytes contained in the deposit)
  • the digital information unit preferably comprises at least one digital computer having sufficient digital storage capacity for storage of the potentially large amounts of information relating to each deposit
  • the leukocyte cell bank of the invention preferably further comprises an arrangement for digital data retrieval interfaced with the digital information unit for retrieving selected information stored in the digital information unit
  • the data retrieval arrangement may be integrated with the digital computer Remote access of the digital information via the telephone or the internet may also be provided and may permit rapid and convenient access of the information on a global basis
  • the invention finds application in all forms of therapy and prophylaxis in which the administration of (treated or untreated) autologous leukocytes is indicated (i e desirable from a therapeutic perspective)
  • a leukocyte deficiency is deemed to have arisen
  • leukocyte deficiencies in which the invention finds medical application encompass a very broad spectrum of diseases, syndromes, disorders, conditions and infections
  • a leukocyte deficiency in the special, broad sense defined above, can arise in circumstances where an individual has acquired a disease, syndrome, disorder, condition or infection involving leukocyte dysfunction as well as in circumstances where an individual has acquired a disease, syndrome, disorder, condition or infection in which the endogenous leukocyte component is seemingly normal but in which alteration, augmentation or stimulation of the normal endogenous leukocyte activity is nevertheless indicated/required
  • a leukocyte deficiency as herein defined may be deemed to have arisen either as a result of a non-specific loss of T- and or B-cells, or as a result of a loss or deficiency of a particular T- and/or B-cell clonal population
  • diseases, syndromes, disorders, conditions or infections are collectively defined herein as leukocytic deficiencies
  • the processes of the invention are employed to create a leukocyte composition (e g forming part of a leukocyte cell bank) from a blood sample from a healthy individual donor
  • a leukocyte composition e g forming part of a leukocyte cell bank
  • the invention is used to create a cellular resource of healthy leukocytic tissue from an individual donor that can be restored to that donor individual should the individual acquire a leukocytic deficiency at a later date
  • the invention exploits the fact that many leukocytic deficiencies occur as part of a temporal sequence of events (which may or may not be causally interrelated), so that the creation of a leukocyte cell bank at a point in time predating onset of the leukocytic deficiency constitutes a therapeutic resource which can later be used restoratively
  • the therapeutic and prophylactic uses of the invention encompass a very broad spectrum of diseases, syndromes, disorders, conditions and infections
  • the invention may find application in the treatment of various infections
  • the endogenous leukocyte activity may be normal (or responding normally) but its alteration, augmentation or stimulation is nevertheless desirable
  • the endogenous leukocyte activity is dysfunctional as a direct consequence of infection
  • Infections which may be treated or prevented according to the invention include bacterial, fungal or viral infections, or infections by any other organism e g a protozoan, nematode, insect or other parasite
  • CD4 + cells can be collected from an individual when healthy or non-infected, and stored for subsequent transplantation into said individual when HIV infection manifests itself or when AIDS develops, or CD4 + cell count falls etc Such a procedure may be attractive to an individual with a life-style likely to place them at risk from contracting HIV infection
  • the invention may find application in the treatment and prophylaxis of various malignancies in general, any malignant or pre-mahgnant condition, proliferative or hyper-pro ferative condition or any disease arising or deriving from or associated with a functional or other disturbance or abnormality in the cells or tissues of the body
  • the invention is not limited to any one type of proliferative disease (e g leukaemias, lymphomas, carcinomas or sarcomas), nor is it restricted to specific oncogenes or tumour-suppressor gene epitopes such as prostate-specific antigen 1 or prostate-specific antigen 2, her-2/new, ras, myc, myb, fos, fas, retinoblastoma, p53 etc or other tumour cell marker epitopes that are presented in an HLA class I antigen restricted fashion or other such way so as to be identifiable by a leukocyte
  • All cancers such as leukaemia, lymphoma, breast, stomach, colon, rectal, lung, liver, uterine, testicular, ovarian, prostate and brain tumours such as gliomas, astrocytomas and neuroblastomas, sarcomas such as rhabdomyosarcomas and fibrosarcomas are included for the therapy or prophylaxis
  • the present invention finds application in the treatment or prophylaxis of breast cancer, colon cancer, lung cancer and prostate cancer It also finds application in the treatment or prophylaxis of cancers of the blood and lymphatic systems (including Hodgkin's Disease, leukemias, lymphomas, multiple myeloma, and Waldenstrom's disease), skin cancers (including malignant melanoma), cancers of the digestive tract (including head and neck cancers, cesophageal cancer, stomach cancer, cancer of the pancreas, liver cancer, colon and rectal cancer, anal cancer), cancers of the genital and urinary systems (including kidney cancer, bladder cancer, testis cancer, prostate cancer), cancers in women (including breast cancer, ovarian cancer, gynecological cancers and chonocarcinoma) as well as in brain, bone carcinoid, nasopharyngeal, retrope toneal, thyroid and soft tissue tumours It also finds application in the treatment or prophylaxis of cancers of unknown primary site
  • the leukocyte composition administered may be derived from a single blood sample, or may constitute a pool of leukocyte compositions derived from a plurality of different blood samples taken from a donor individual at different times
  • the leukocyte composition administered may constitute all or a fraction of the deposited material, but preferably constitutes only a fraction thereof in order that multiple dosing can be achieved, optionally following cellular expansion of the residue (for example, T cell numbers may be increased by in vitro expansion using standard methods)
  • the number of mature T-cells administered is at least 0 01 x 10 8 , more preferably at least 0 1 x 10 8 , more preferably at least 1 x 10 8 (e g at least 1-10 x 10 8 )
  • the preferred ranges are 0 01 x 10 8 to 10 10 mature T lymphocytes, such as 0 1 x 10 8 to 10 10 , 1 x 10 8 to 10 10 or 1 x 10 9 to 10 10 mature T lymphocytes
  • the mature T-cell sample acquired for autotransplantation is at least 0 01 x 10 8 , generally in the range of 10 8 - 10 10 CD3 + mature T-cells, preferably 2 x 10 8 - 10 10 , more preferably 3 x 10 8 - 10 10 CD3 + and even more preferably 4-5 x 10 8 - 10 10 CD3 + mature T-cells
  • each sample prepared for autotransplantation contains 3 x 10 8 CD3 + mature T-cells, more preferably 5 x 10 8 and even more preferably 1x10 9 CD3 + mature T-cells If sufficient resources of blood are available from an individual, even more preferably still 4-5 x 10 9 CD3 * mature T-cells or 10 10 CD3 + mature T- cells may be used
  • the mature T-cell subpopulation sample acquired for autotransplantation which is CD3 + and CD8 + is at least 0 01 x 10 8 , generally in the range of 0 25 x 10 8 - 0 25 x 10 10 , and more preferably 0 5 x 10 8 - 0 25 x 10 10 , and even more preferably 0 75 x 10 8 - 0 25 x 10 10 , and even more preferably still 0 75 x 10 8 - 0 25 x 10 10 or 1 00 - 1 25 x 10 8 - 0 25 x 10 10
  • Specific CD3 + and CD8 + cell numbers in each sample prepared for grafting is conveniently of the order of 0 2 x 10 8 , preferably 0 4 x 10 8 , or more preferably 1 x 10 8 , or still more preferably 2 x 10 8 , or more preferably 3 x 10 8 , or more preferably 5 x 10 8 If sufficient resources from an individual are available, 1 x 10 9 ,
  • the mature T-cell subpopulation sample acquired for autologous transplantation which is CD3 + and CD4 + is at least O 01 x 10 8 , generally in the range of 0 I x 10 8 - 0 5 x 10 10 , and more preferably 0 65 x 10 8 - 0 5 x 10 10 , and even more preferably 0 85 x 10 8 - 0 5 x 10 10 , and even more preferably still 1 x 10 8 - 0 5 x 10 10 or 1 8 - 3 6 x 10 8 - 0 5 x 10 10
  • Specific CD3 + and CD4 + cell numbers in each sample prepared for grafting is conveniently of the order of 0 2 x 10 10 , preferably 0 3 x 10 8 , or more preferably 0 4 x 10 8 , 0 5x10 8 , 1 x 10 8 , 2 x 10 8 , 3 x 10 8 , 4 x 10 8 , or more preferably 5 x 10 8 If sufficient resources from an
  • the mature T-cell natural killer subpopulation sample acquired for autotransplantation which is CD3 + and CD16/56 + is at least 0 01 x 10 8 , generally in the range of 0 01 x 10 8 - 0 5 x 10 10 , preferably 0 02 x 10 8 - 0 5 x 10 10 , more preferably 0 03 x 10 8 - 0 5 x 10 10 , and even more preferably still 0 5 x 10 8 -0 5 x 10 10 or 0 5-2 x 10 8 to 0 5 x 10 10
  • Specific CD3 + and CD16/56 + cell numbers in each sample prepared for grafting is conveniently of the order of 0 01 x 10 8 , 0 2 x 10 8 , 0 3 x 10 8 , 0 5 x 10 8 , 1 x 10 8 , 2 x 10 8 , 3 x 10 s , 5 x 10 8 , or more preferably, if sufficient resources are available, I x 10 9
  • the mature lymphocyte cell sample may preferably include B cells such as CD19 + B lymphocytes
  • the mature B-cell sample included in the T-cell sample may be at least 10 7 , 10 8 or 10 9 , generally in the range of 10 7 -10 10 mature B-cells and preferably 2 x 10 7 - 10 10 mature B-cells, more preferably 3 x 10 7 - 10 10 mature B- cells, and even more preferably 4-5 x 10 7 - 10 10 mature B-cells
  • B-cells in autograft is conveniently of the order of 3 x 10 7 , preferably 5 x 10 8 , more preferably 1 x 10 8 mature B-cells, and even more preferably still 4-5 x 10 9 or 10 10 mature B-cells
  • the lymphocyte cell sample may preferably include dendritic cells
  • the dendritic cell sample may be at least 10 7 , 10 8 or 10 9 in number, and generally in the range of 10 7 - 10 10 dendritic cells and preferably 2 x 10 7 - 10 10 cells, more preferably 3 x 10 7 - 10 10 cells, and even more preferably 4-5 x 10 7 - 10 10 cells
  • dendritic cells in an autograft is conveniently of the order of 3 x 10 7 , preferably 5 x 10 8 more preferably 1 x 10 8 , and even more preferably still 4-5 x 10 9 or 10 10 mature B-cells

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Primary Health Care (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
  • Vascular Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

La présente invention concerne un procédé pour produire une banque de leucocytes destinés à une thérapie de transplantation autologue en cas de besoin (contingent autologous transplantation / CAT), le procédé comprenant les étapes suivantes: mise à disposition d'un échantillon de sang d'un donneur sain; séparation sélective de leucocytes de l'échantillon; collecte des leucocytes séparés dans un récipient de réception; transfert d'au moins deux parties aliquotes des leucocytes séparés dans des récipients de stockage doubles indépendants, chaque récipient de stockage contenant, ou étant en communication fluidique avec, un milieu de cryoconservation; mélange de chaque partie aliquote avec le milieu de cryoconservation à l'intérieur de chaque récipient de stockage, pour permettre la cryoconservation des parties aliquotes à l'intérieur de chaque récipient de stockage; dépôt, pour permettre leur retrait, de chacun des récipients de stockage contenant les parties aliquotes de leucocytes conservés, dans au moins deux systèmes de stockage indépendants, afin de produire une banque de leucocytes qui se caractérise par un dépôt redondant; les étapes étant mises en oeuvre dans un système fermé ou fonctionnellement fermé, et appliquées de façon itérative à une série d'échantillons de sang issus de différents donneurs sains. Le procédé comprend également l'enregistrement numérique d'informations obtenues de chaque donneur, dans une unité d'informations numériques, pour permettre la mise en correspondance du dépôt de leucocytes et du donneur pour une transplantation autologue ultérieure.
EP04768677A 2003-09-30 2004-09-28 Banque de cellules pour transplantation de leucocytes autologue en cas besoin Ceased EP1677809A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09011764A EP2133087A3 (fr) 2003-09-30 2004-09-28 Banque de cellules pour transplantation de leucocyte autologue contingente

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0322806.1A GB0322806D0 (en) 2003-09-30 2003-09-30 Cell bank for contingent autologous leukocyte transplantation
PCT/GB2004/004134 WO2005032564A1 (fr) 2003-09-30 2004-09-28 Banque de cellules pour transplantation de leucocytes autologue en cas besoin

Related Child Applications (1)

Application Number Title Priority Date Filing Date
EP09011764A Division EP2133087A3 (fr) 2003-09-30 2004-09-28 Banque de cellules pour transplantation de leucocyte autologue contingente

Publications (1)

Publication Number Publication Date
EP1677809A1 true EP1677809A1 (fr) 2006-07-12

Family

ID=29287072

Family Applications (2)

Application Number Title Priority Date Filing Date
EP04768677A Ceased EP1677809A1 (fr) 2003-09-30 2004-09-28 Banque de cellules pour transplantation de leucocytes autologue en cas besoin
EP09011764A Withdrawn EP2133087A3 (fr) 2003-09-30 2004-09-28 Banque de cellules pour transplantation de leucocyte autologue contingente

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP09011764A Withdrawn EP2133087A3 (fr) 2003-09-30 2004-09-28 Banque de cellules pour transplantation de leucocyte autologue contingente

Country Status (3)

Country Link
EP (2) EP1677809A1 (fr)
GB (1) GB0322806D0 (fr)
WO (1) WO2005032564A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3069980A1 (fr) * 2017-07-24 2019-01-31 Arteriocyte Medical Systems, Inc. Procedes de preparation de fractions biologiques soumises a un echange en phase liquide et dispositifs destines a etre utilises dans la mise en oeuvre de ceux-ci

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3655123A (en) 1966-08-08 1972-04-11 Us Health Education & Welfare Continuous flow blood separator
US3489145A (en) 1966-08-08 1970-01-13 Surgeon General Of The Public Method and apparatus for continuous separation of blood in vivo
US3802432A (en) 1972-05-18 1974-04-09 I Djerassi Apparatus for filtration-leukopheresis for separation and concentration of human granulocytes
US3892236A (en) 1973-04-02 1975-07-01 Isaac Djerassi Apparatus for filtration-leukopheresis for separation and concentration of human granulocytes
US4111199A (en) 1977-03-31 1978-09-05 Isaac Djerassi Method of collecting transfusable granulocytes by gravity leukopheresis
SE416617B (sv) 1979-03-28 1981-01-26 Johansson A S Anordning vid blodseparation genom utklemning av blodkomponenter ur en blodpase
DE3417892A1 (de) 1984-05-14 1985-11-14 Npbi Nederlands Produktielaboratorium Voor Bloedtransfusieapparatuur En Infusievloeistoffen B.V., Emmer-Compascuum Vorrichtung zum entfernen einer blutplasmaschicht und einer buffycoatschicht aus einem flexiblen beutel mit blutfuellung
US5686238A (en) * 1992-02-10 1997-11-11 Baxter International Inc. Method and device for testing blood units for viral contamination
WO1995010291A1 (fr) * 1993-10-08 1995-04-20 Cellpro Ii Procedes de collecte et de cryoconservation de granulocytes humains
JPH07328099A (ja) * 1994-06-09 1995-12-19 Terumo Corp バッグ連結体および血液成分の分離・移送方法
SE503106C2 (sv) 1994-07-01 1996-03-25 Asea Brown Boveri Lastkommuterad synkronmotordrift
GB9422236D0 (en) 1994-11-03 1994-12-21 Stringer Bradley M J Transgenic organisms and their uses
SE505621C2 (sv) 1995-03-21 1997-09-22 Omega Medicinteknik Ab Sätt och extraktor för buffycoatskördning från centrifugerade kolaberbara blodbehållare
GB2343679A (en) 1998-11-16 2000-05-17 Alison Miriam Davies Autologous transplantation and method for making cells dormant
US6652475B1 (en) * 1999-07-07 2003-11-25 Mission Medical, Inc. Automated blood component separation system
AU4771600A (en) 2000-05-16 2001-11-26 Alison Davies Cells, culture methods and their uses
FR2811272B1 (fr) * 2000-07-05 2002-09-27 Sicma Aero Seat Siege pour avion a repose jambes et repose pieds reglables
BRPI0312436A2 (pt) * 2002-06-19 2016-06-28 Northwest Biotherapeutics Inc dispositivo de filtragem de fluxo tangencial e métodos para enriquecimento em leucócito
US20070148772A1 (en) * 2003-06-21 2007-06-28 Lifeforce Group Plc Leukocyte cell banks

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005032564A1 *

Also Published As

Publication number Publication date
WO2005032564A1 (fr) 2005-04-14
EP2133087A3 (fr) 2010-01-20
EP2133087A2 (fr) 2009-12-16
GB0322806D0 (en) 2003-10-29

Similar Documents

Publication Publication Date Title
US20080103428A1 (en) Apheresis Tubing Set
US20090324567A1 (en) Leukocyte Cell Banks
De Wildt‐Eggen et al. Reactions and platelet increments after transfusion of platelet concentrates in plasma or an additive solution: a prospective, randomized study
US20100221230A1 (en) Elective Collection and Banking of Autologous Peripheral Blood Stem Cells
US20070212674A1 (en) Blood Co-Processing For Contingent Autologous Leukocyte Transplantation
Cannas et al. Supportive care in patients with acute leukaemia: historical perspectives
Cid et al. Leukocytapheresis in nonmobilized donors for cellular therapy protocols: evaluation of factors affecting collection efficiency of cells
Gilcher et al. Apheresis: principles and technology of hemapheresis
EP1817067A1 (fr) Sac de prelevement de sang pour creer des banques de leucocytes
US20190224494A1 (en) Apparatus and method for batch photoactivation of mononuclear cells with cryopreservation
Worel et al. Serial granulocytapheresisunder daily administration of rHuG–CSF: effects on peripheral blood counts, collection efficiency, and yield
EP1677809A1 (fr) Banque de cellules pour transplantation de leucocytes autologue en cas besoin
Greinix et al. Extracorporeal photopheresis: cellular photoimmunotherapy
WO2001088099A1 (fr) Cellules, procedes de mise en culture et leurs utilisations
Wuest et al. Removal of ABO‐incompatible red cells from lymphocytapheresis and granulocytapheresis components before transfusion
WO2005041991A1 (fr) Transplantation de globules blancs
Elfath et al. Quality and clinical response to transfusion of prestorage white cell‐reduced apheresis platelets prepared by use of an in‐line white cell‐reduction system
McCullough Principles of transfusion support before and after hematopoietic cell transplantation
Daly Oncology Grand Rounds: Platelet transfusion—clinical applications in the oncology setting
Dutcher Platelet and granulocyte transfusion
Rebulla Platelet support of patients with hematological malignancies
Bird et al. Leucocyte depletion of blood components-guidelines of the blood transfusion services of South Africa
Cullis et al. A technique to reduce lymphocyte contamination of plateletapheresis products collected with a centrifugal blood cell separator
Flatow et al. Preparation of platelet concentrates for transfusion employing adenosine diphosphate
Niranjan et al. Utility of compatible non identical blood components in transfusion services

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20060502

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PL PT RO SE SI SK TR

17Q First examination report despatched

Effective date: 20061012

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 20090516