EP1109921A1 - Recepteurs de fusion specifiques a l'antigene prostatique specifique membranaire et ses utilisations - Google Patents

Recepteurs de fusion specifiques a l'antigene prostatique specifique membranaire et ses utilisations

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Publication number
EP1109921A1
EP1109921A1 EP99945508A EP99945508A EP1109921A1 EP 1109921 A1 EP1109921 A1 EP 1109921A1 EP 99945508 A EP99945508 A EP 99945508A EP 99945508 A EP99945508 A EP 99945508A EP 1109921 A1 EP1109921 A1 EP 1109921A1
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Prior art keywords
psma
cells
cytoplasmic domain
fusion
transduced
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EP99945508A
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German (de)
English (en)
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EP1109921A4 (fr
Inventor
Michel Sadelain
Neil H. Bander
Michael Gong
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Sloan Kettering Institute for Cancer Research
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Sloan Kettering Institute for Cancer Research
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Publication of EP1109921A1 publication Critical patent/EP1109921A1/fr
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Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70517—CD8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70521—CD28, CD152
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/027—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a retrovirus

Definitions

  • This invention relates to fusion receptors for prostate-specific membrane antigen (PSMA), and to uses thereof in the treatment of prostate cancer, other cancers expressing PSMA and tumor neovasculature.
  • PSMA prostate-specific membrane antigen
  • the inventions provides fusion receptors, nucleic acids encoding these fusion receptors, and transduced cells expressing the fusion receptors, as well as methods of using the transduced cells.
  • T cell immunity Destruction of immunological targets requires T lymphocyte recognition via the T cell receptor (TCR) of antigenic peptides presented in the context of major histocompatibility complex (MHC) molecules on antigen- presenting cells (APC).
  • TCR T cell receptor
  • MHC major histocompatibility complex
  • APC antigen- presenting cells
  • T cell costimulation results from an interaction of the T cell surface receptor CD28 with the costimulatory hgand B7, which is p ⁇ maiily expressed on the surface of professional APCs and activated B cells leading to IL-2 secretion and clonal expansion of the activated T cells
  • CD28 costimulatory hgand B7
  • signals transduced by the CD28 receptor determine whether TCR occupancy results in a pioductive immune response or clonal anergy Therefore, one factor accounting for the pooi immunogenicity of MHC-expressmg tumors is that, despite presentation of potentially immunogemc peptides lithe context of MHC molecules, tumors lack the costimulatory molecule B7, and thus fail to elicit a full activation of T cells and therefore an effective anti-tumoi T cell response
  • the introduction of the B7 molecule (CD28 hgand) in tumor cells is one discussed therapy today (melanoma Townsend et al, 1993, Chen et al, 1992
  • T cells can lecogmze and lyse tumor cells provided that they bind to the tumor cells and are appiop ⁇ ately activated T cell activation operates according to the two signal model, which states that lymphocytes require for optimal activation both an antigen-specific signal delivered through the antigen receptor and a second antigen nonspecific or costimulatory signal T cell costimulatory pathways determine whether TCR complex engagement results in functional activation or clonal anergy of CD4 T cells
  • T lymphocytes One means of generating tumor-specific T lymphocytes is then modification by gene transfer of tumor-specific fusion molecules
  • the mtioduction of chime ⁇ c molecules m T cells combining tumor specific single chain variable fragment (scFv) with signal transduction domains of TCR related activation molecules is reported by a number of groups (Eshar et al, Springer Semin. Immunopathol. 18: 199-209 (1993)).
  • scFv tumor specific single chain variable fragment
  • These genetically modified T cells are able to target tumor cells and to destroy them in vitro, but based on the two signal model for T cell activation, the reinfusion of these transduced T lymphocytes is limited by the incomplete activation signal after antigen recognition and clonal expansion in vivo is not successful.
  • antigen dependent IL-2 secretion can be stimulated in vitro in Jurkat cells expressing a chimeric molecule formed from an antigen-specific scFv and the ⁇ -chain of CD3, when the cells are exposed to the antigen in the presence of anti-CD28 or ionomycin as a costimulatory signal.
  • Cells expressing both chimeric molecules displayed responses to either antigen in the presence of appropriate costimulatory molecules. Alvarez- Vallina et al. suggests that these results offer the possibility that addition of antigen-specific CD28 mediated signaling could improve adoptive immunotherapies.
  • T-cell receptors have not been shown to function in human peripheral blood lymphocytes (PBL) and in particular in the T cells of actual cancer patients.
  • PBL peripheral blood lymphocytes
  • the present invention provides a fusion receptor composition which is effective to promote a cellular immune response to a target antigen in vivo when the fusion receptor is expressed by T lymphocytes.
  • the target antigen is prostate-specific membrane antigen (PSMA)
  • PSMA prostate-specific membrane antigen
  • PSMA-scFv optional connector : cytoplasmic domain.
  • the PSMA-scFv in this structure is a single chain antibody cloned from the V region genes of a hybridoma specific for PSMA.
  • the optional connector region is provided to give a spacing between the PSMA-scFv and the cytoplasmic domain, such that both can retain substantial function.
  • a suitable connector is the CD8 hinge, although other connectors of greater or lesser length might be used.
  • the cytoplasmic domain is included to direct the function of the fusion receptor.
  • One exemplary cytoplasmic domain which can be used in the fusion receptor of the invention is a T cell receptor ⁇ -chain cytoplasmic domain.
  • an expression vector encoding the fusion receptor is transduced into primary T lymphocytes obtained from an individual to be treated, for example an expression vector encoding the PSMA-scFv containing fusion receptor is suitably transduced into cells from a human patient who has been diagnosed with prostate cancer.
  • the transduced lymphocytes are returned to the patient where cells expressing the fusion receptor secrete interleukin 2 and proliferate in response to PSMA- positive cells.
  • the resulting cytotoxic lymphocytes specifically lyse cells expressing PSMA and thus can be used to target PSMA-positive tumor cells.
  • NK cells natural killer cells or other immune effector cells allows these cells to target any tissue (including tumor tissue) expressing PSMA.
  • tissue including tumor tissue
  • NK cells can be used to treat prostate cancer, other cancers expressing PSMA and tumor-associated neovasculature.
  • Fig. 1 shows the structure of a retroviral vector Pz-1 including a gene for a PSMA-specific fusion receptor in accordance with the invention
  • Figs. 2 A-E show cytotoxicity of Pz-1 transduced PBL with respect to various target cells
  • Fig. 3 shows the time course for cocultivation of transduced T cells with fibroblasts
  • Fig. 4A shows T cells proliferation in coculture with various types of fibroblast cells
  • Fig. 4B shows cell lysis by T cells after prior exposure to coculture conditions
  • Fig. 5 shows IL-2 production by transduced T cells in coculture with various types of fibroblast cells.
  • the present invention provides fusion receptors which are useful in the generation of a cellular immune response to cells which express PSMA.
  • fusion receptors have the general structure:
  • PSMA-scFv optional connector : cytoplasmic domain. This structure is produced by expression in transduced cells of a DNA sequence encoding the ammo acid sequence of the fusion receptor
  • PSMA-scFv is a single chain antibody cloned from the V region genes of a hybridoma specific for PSMA
  • a suitable hybridoma for this purpose is J591, which is described m Liu et al , Cancer Res 57 3629-3635 (1997), although other hyb ⁇ domas which produce monoclonal antibodies specific to PSMA could also be employed The production of such hyb ⁇ domas has become routine, and the procedure will not be repeated here
  • V H variable region heavy chain
  • V L variable region light chain
  • the cytoplasmic domain portion of the general formula set forth above is selected to enhance the characteristics of the fusion leceptoi for purposes of promoting a cellular immune response to the antigen recognized by the scFv portion of the fusion receptor
  • the cytoplasmic domain is the cytoplasmic domain of a molecule which functions as a transducei of a mammalian immune response in the presence of an MHC- peptide complex or costimulatory factoi
  • Representative, non-limitmg examples of cytoplasmic domains which may be employed m the present invention include the ⁇ -cham cytoplasmic domain, the CD28 cytoplasmic domain (particularly a fragment spanning ammo acids 336 to 663 of CD28 cDNA), 41BB, CD40, ICOS and trance
  • the cytoplasmic domain is the ⁇ -chain derived the TCR complex
  • the fusion receptor of the invention closely mimics a native TCR In this case, it might be expected that binding of an antigen to the scFv
  • the fusion receptors of the invention may include othei cytoplasmic domains
  • CD28 can be used as the cytoplasmic domain to enhance T-cell activation, survival and prohfeiation
  • a preferred CD28 moiety is one which spans ammo acids 336 to 663 of CD28 cDNA, in which case no connector is needed to retain functon PSMA-fusion receptors incorporating 41BB as the cytoplasmic domain ha ⁇ e also been prepared
  • Both the PSMA-CD28 and the PSMA-41 BB fusion receptors have been made and tested m the same experimental model used with the PSMA- ⁇ chain fusion receptor In both cases, sustained proliferation was obseived in both human CD4 and CD8 primary T cells (PBL) m the presence of PSMA ⁇ cells, with moie sustained proliferation being provided by the PSMA-41BB fusion receptor High production of IFN- ⁇ and IL-2 was observed, for PSMA-41BB and PSMA-CD28 transduced, respectively In each of the experiments performed
  • the function of the connector is to act as a spacer so that both the scFv and the cytoplasmic domain can be functionally oriented within the membrane of the transduced cell.
  • One exemplary connector is the CD8 hinge, although other connectors of greater or lesser length could be used. In some cases, such as using the CD28 fragment described herein, no connector is required to permit the molecules to assume the desired orientation.
  • the chimeric fusion receptors are introduced into the individual to be treated (preferably a human) in one of two ways. Gene transfer can be carried out into bone marrow cells, either in vivo or ex vivo, or into immune effector/inflammatory cells such as T- lymphocytes or NK cells. Gene transfer may also be carried out into antigen presenting cells, particularly dendritic cells. In the case of dendritic cells, CD40 and trance are the preferred cytoplasmic domain.
  • a preferred approach to this gene transfer is using retroviral vectors encoding the fusion receptor.
  • a particularly preferred approach utilizes an SFG retroviral vector (Riviere et al., Proc. NatlAcad Sci. (USA) 92: 6733-6737 (1995)) transduced into patient PBL using gibbon ape leukemia virus (GALV) envelope-pseudotyped virions. (Gallardo et al., Blood 90: 952-957 (1997).
  • the PSMA-specific fusion receptor of the present invention is useful in the treatment of prostate cancer.
  • PSMA is also found in the neovasculature of renal cell, urothelial, colon, breast and lung carcinomas, melanomas and some sarcomas
  • the PSMA-specific fusion receptor of the invention has broader applicability.
  • the present application describes a method for treatment of cancers in which the cancer cells or neovasculature are characterized by expression of PSMA, comprising administering to a patient suffering from such a cancer patient-derived lymphocytes which express with a PSMA fusion receptor having the structure
  • PSMA-scFv optional connector : cytoplasmic domain.
  • administration is intended to encompass both in vivo methods, in which the fusion receptor is introduced into the lymphocytes without first removing them from the patient, and ex vivo methods where the patient-derived lymphocytes are obtained from the patient, transduced with the PSMA-specific fusion receptor and then reintroduced to the patient.
  • the transduced lymphocytes are introduced in an amount to provide therapeutic benefit. Where sufficient clonal expansion of the transduced lymphocytes occurs in vivo, a long-term immunity to the tumor cells may be induced after a single administration. If the transduced lymphocytes are less stable, multiple infusions may be required to obtain remission of a particular cancer, and long-term protection may not be achieved. In either case, the determination of the appropriate therapeutic regimen is a matter of routine developed in the course of clinical trials.
  • Example 1 PSMA-scFv was created by cloning the immunoglobulin genes from the J591 hybridoma encoding the variable region of the heavy chain (V H and the variable region of the light chain (V L ).
  • the V H and V L genes were cloned using the technique previously described by Orlandi et al., supra. Briefly, mRNA was isolated from the J591 hybridoma cell line and reverse transcribed into cDNA using a reverse transcriptase polymerase chain reaction (RT- PCR) kit obtained from Pharmacia, Pisacatway, NJ.
  • RT- PCR reverse transcriptase polymerase chain reaction
  • V H gene Sequence analysis of the V H gene confirmed an appropriate open reading frame. However, the V L gene sequence analysis revealed a stop codon in the anticipated reading frame. The sequences of the genes encoding the J591 monoclonal antibody heavy and light chain were compared to the sequences of the cloned products, and several discrepancies were noted between the V L sequences. The major difference was that the primer pair used deleted a nucleotide from the actual sequence, resulting in an open reading frame shift that produced a stop codon. Nucleotide sequence corrections in the V L product were made using corrective primers based on the actual sequences and using these primers in a second PCR amplification utilizing the obtained V, sequence as a template. The corrective primers were: V L backward: GAAGAAGATCJG CATTGTGATGACCAGTCTC CAAATTCATG Seq. ID. No. 5
  • an oligonucleotide encoding the human CD8 leader sequence was cloned to the 5'-end of the V H gene, and the 3'-end of the V,, gene was cloned to an oligonucleotide encoding a (gly-ser 2 ) 5 linker followed by the V L gene, creating the PSMA- specific scFv.
  • the scFv was then cloned to the CD8 hinge and transmembrane domains, followed by the T cell receptor ⁇ -chain cytoplasmic domain to create Pz-1, a PSMA-specific scFv/ ⁇ -chain chimeric T-cell receptor.
  • the Pz-1 fusion gene was then cloned into the SFG retroviral vector (Riviere et al, supra) as illustrated in Fig. 1.
  • Example 2 The SFG retroviral vector containing Pz-1 was transduced into PBL's harvested from five human patients suffering from prostate cancer with a variety of clinical stages using GALV envelope pseudo typed virions as previously described. Gallardo et al., supra. The clinical status of three representative patients is summarized in Table 1.
  • the age is the current age of the patient, the time since dx is the time elapsed between date of diagnosis of prostate cancer and PBL harvest; GG is the Gleason grade of the patient's most recent prostate cancer pathology; stage at dx is the clinical stage at the time of original diagnosis; RRP in the treatment column stands for radical retropubic prostatectomy; current stage is the current clinical or pathological state and current PSA is the most recent serum prostate specific antigen (PSA) level.
  • PSA serum prostate specific antigen
  • the PBL were expanded 4 to 14 days in the presence of interleukin-2 (IL-2).
  • IL-2 interleukin-2
  • Gene transfer efficiency was monitored by FACS analysis using a FITC-conjugated Pz-1 idiotype-specific antiserum. After incubation with the FITC labeled antiserum, the cells were washed incubated with 10% normal mouse serum, and stained with a PE-conjugated anti-CD8 mAb. The gene transfer efficiency observed varied between 20% and 50% in both CD8" and CD4 * cells for Pz-1 and controls.
  • Example 3 Cytotoxic T lymphocyte (CTL) assays were performed on the human prostate cancer cell line LNCaP which abundantly expresses PSMA. In order to confirm that the cytotoxicity was PSMA-specific, PSMA was expressed in PC-3, a PSMA-negative human prostate cancer cell line and EL-4, a murine thymoma cell line. PBL from the three patients of Table 1 were transduced with either Pz-1 or NTP, a mutated human low-affinity nerve growth factor receptor used as a control cell surface marker. (Gallardo et al., supra). Transduction efficiency (%TR) measured as described above, and the fraction of CD8 + and CD56 + cells on the day of the CTL assay are reported in the common legend of Fig. 2.
  • CTL Cytotoxic T lymphocyte
  • E:T effector to target
  • PBL transduced with Pz-1 but not NTP effectively lysed PSMA + targets.
  • Example 4 To further assess the response of Pz-1 transduced primary T cells to PSMA, we investigated whether Pz-1 + PBL could undergo proliferation upon engagement with cell- bound PSMA and sustain thereafter their cytolytic potential.
  • a cocultivation system was established in which transduced T cells were cultured with a layer of irradiated NIH3T3 fibroblasts expressing various combinations of PSMA and B7.1 for four days with periodic sampling to measure levels of IL-2 as illustrated in Fig. 3.
  • FACS cell counts using FITC- conjugated Pz-1 idiotype specific antibody and with either anti-CD4 or anti-CD8 were performed after four days of co-cultivation, and again 4 days later.
  • the transduced T cell count was derived by multiplying the percentage of CD4 + Pz-T or CD8 ⁇ Pz-l ⁇ double positive cells by the number of viable cells.
  • the results are shown in Fig. 4A, where /B7+PSMA, /PSMA and /B7 refer to the molecules expressed by the fibroblast layer.
  • PSMA induced proliferation of Pz-1 transduced T-cells increasing the number of cells 6-8 fold after 4 days, and these transduced cells destroyed PSMA + fibroblast layers within 48 hours, while the PSMA " layers remained intact during the entire 4-day cocultivation. By day 8, however, the absolute number of Pz-1 + cells dropped to 2-3 fold above initial levels.
  • B7.1 (CD80) was transduced into PSMA + and PSMA " fibroblasts.
  • Example 5 To test whether cytotoxic T cells retain their cytotoxic potential after restimulation with antigen, T cells were harvested 12-17 days after the start of coculture with fibroblast monolayers expressing PSMA and B7.1 and retested in the CTL assay. As shown in Fig. 5, expanded Pz-1 transduced T cells remained fully capable of lysing PSMA " target cells. Furthermore, the expanded Pz-1 + cells were capable of a second round of proliferation and IL-2 and IFN- ⁇ secretion when reexposed to PSMA + B7.1 + fibroblasts.
  • T cells bearing artificial TCRs the prospect of apoptotic cell death or anergy upon restimulation could be compounded by partial T cell activation if chimeric receptors fail to adequately recruit downstream signaling molecules. Faulty T cell activation could result in the induction of immune tolerance and the neutralization of the infused effector T cells. Such phenomenon could in part explain in vivo findings obtained with T cells expressing an ErbB- 2 specific- ⁇ chain fusion receptor, required repeated high dose intra-tumoral administration to effectively eliminate established tumors. Alternschmidt et al, J. Immunol. 159: 5509-5515 (1997).
  • Example 2 In order to prepare a fusion receptor in which the cytoplasmic domain is derived from CD-28, the procedure of Example 1 was repeated only using a CD28 fragment in place of the ⁇ -chain segment. The CD28 cDNA fragment was obtained as follow.
  • a segment of the human CD28 cDNA that encodes part of the extracellular, the transmembrane, and the cytoplasmic domains was amplified by PCR from the plasmid pbsCD28, using the upstream primer
  • primers contain Notl and BamHI sites respectively for the insertion of the PCR product in the retroviral Vector SFG.
  • the CD28 fragment was ligated into the Notl an BamHI sites of the retroviral vector SFG, containing the CD8 ⁇ leader sequence, followed by the single chain gene, encoding the V H and V L domains of the PSMA-specific antibody

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Abstract

Une composition de récepteur de fusion efficace pour stimuler une réponse cellulaire immunitaire à l'antigène prostatique spécifique membranaire (PSMA) in vivo lorsque le récepteur de fusion est exprimé par les lymphocytes T présente la structure: PSMA-scFv: connecteur: domaine cytoplasmique. Le PSMA-scFv dans cette structure est un anticorps monocaténaire cloné à partir des gènes de régions V d'un hybridome spécifique à PSMA. La région de connecteur est prévue pour former un espace entre le PSMA-scFv et le domaine cytoplasmique, de manière que l'un et l'autre puissent conserver une fonction substantielle. Un connecteur approprié est la charnière CD8, bien que d'autres connecteurs d'une longueur supérieure ou inférieure puissent être utilisés. Le domaine cytoplasmique est inclus pour diriger la fonction du récepteur de fusion. Un domaine cytoplasmique cité à titre d'exemple pouvant être utilisé dans le récepteur de fusion de l'invention est le domaine cytoplasmique à chaîne z du récepteur des lymphocytes T. Un vecteur d'expression codant le récepteur de fusion est transduit dans des lymphocytes T primaires prélevés sur un individu à traiter. Les lymphocytes transduits sont retournés au patient chez qui les cellules exprimant le récepteur de fusion sécrètent de l'interleukine 2 et prolifèrent en réponse aux cellules réagissant positivement à PSMA. Les lymphocytes cytotoxiques obtenus lysent spécifiquement des cellules exprimant PSMA et peuvent ainsi être utilisés pour cibler des cellules tumorales réagissant positivement au PSMA et le système néovasculaire.
EP99945508A 1998-09-04 1999-09-03 Recepteurs de fusion specifiques a l'antigene prostatique specifique membranaire et ses utilisations Withdrawn EP1109921A4 (fr)

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PCT/US1999/020349 WO2000014257A1 (fr) 1998-09-04 1999-09-03 Recepteurs de fusion specifiques a l'antigene prostatique specifique membranaire et ses utilisations

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KR100388942B1 (ko) * 2000-07-08 2003-06-25 한화석유화학 주식회사 인체의 피질 흉선 세포 및 백혈병 종양 세포 표면단백질을 인식하는 분절 항체
AUPQ923100A0 (en) * 2000-08-07 2000-08-31 Peplin Research Pty Ltd Treatment of prostate cancer
WO2002040059A2 (fr) * 2000-11-01 2002-05-23 American Foundation For Biological Research, Inc. Procedes et compositions pour induire des reponses immunitaires a mediation cellulaire
EP1427377A4 (fr) * 2001-09-20 2006-04-12 Cornell Res Foundation Inc Methodes et compositions de traitement ou de prevention de troubles cutanes au moyen d'agents de liaison specifiques pour un antigene membranaire specifique de la prostate
US20050215472A1 (en) 2001-10-23 2005-09-29 Psma Development Company, Llc PSMA formulations and uses thereof
EP1448588A4 (fr) 2001-10-23 2006-10-25 Psma Dev Company L L C Anticorps et multimeres de proteines psma
US20130266551A1 (en) 2003-11-05 2013-10-10 St. Jude Children's Research Hospital, Inc. Chimeric receptors with 4-1bb stimulatory signaling domain
US7435596B2 (en) 2004-11-04 2008-10-14 St. Jude Children's Research Hospital, Inc. Modified cell line and method for expansion of NK cell
WO2006036445A2 (fr) 2004-09-24 2006-04-06 Trustees Of Dartmouth College Recepteur nk chimerique et traitement anticancereux
US9249423B2 (en) 2007-02-02 2016-02-02 Yale University Method of de-differentiating and re-differentiating somatic cells using RNA
US10155038B2 (en) 2007-02-02 2018-12-18 Yale University Cells prepared by transient transfection and methods of use thereof
WO2008097926A2 (fr) 2007-02-02 2008-08-14 Yale University Transfection transitoire avec de l'arn
PL2326350T3 (pl) 2008-09-08 2014-03-31 Psma Dev Company L L C Związki do zabijania eksprymujących PSMA, opornych na taksan komórek rakowych
US9273283B2 (en) 2009-10-29 2016-03-01 The Trustees Of Dartmouth College Method of producing T cell receptor-deficient T cells expressing a chimeric receptor
US9181527B2 (en) 2009-10-29 2015-11-10 The Trustees Of Dartmouth College T cell receptor-deficient T cell compositions
SG10201510092QA (en) 2010-12-09 2016-01-28 Univ Pennsylvania Use of chimeric antigen receptor-modified t cells to treat cancer
US9833476B2 (en) 2011-08-31 2017-12-05 The Trustees Of Dartmouth College NKP30 receptor targeted therapeutics
EP2847223B1 (fr) 2012-05-07 2019-03-27 Trustees of Dartmouth College Anticorps anti-b7-h6, protéines de fusion, et leurs procédés d'utilisation
KR102313997B1 (ko) 2013-02-20 2021-10-20 노파르티스 아게 인간화 항-EGFRvIII 키메라 항원 수용체를 사용한 암의 치료
TW201446794A (zh) 2013-02-20 2014-12-16 Novartis Ag 利用抗－ｃｄ１２３嵌合抗原受體工程化ｔ細胞之初級人類白血病有效靶向
US9745368B2 (en) 2013-03-15 2017-08-29 The Trustees Of The University Of Pennsylvania Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy
TWI654206B (zh) 2013-03-16 2019-03-21 諾華公司 使用人類化抗－ｃｄ１９嵌合抗原受體治療癌症
JP6779785B2 (ja) 2013-12-19 2020-11-04 ノバルティス アーゲー ヒトメソテリンキメラ抗原受容体およびその使用
WO2015090229A1 (fr) 2013-12-20 2015-06-25 Novartis Ag Récepteur d'antigène chimérique régulable
US11028143B2 (en) 2014-01-21 2021-06-08 Novartis Ag Enhanced antigen presenting ability of RNA CAR T cells by co-introduction of costimulatory molecules
PL3129470T3 (pl) 2014-04-07 2021-11-29 Novartis Ag Leczenie nowotworu złośliwego z zastosowaniem chimerycznego receptora antygenowego anty-CD19
RU2763795C2 (ru) 2014-04-23 2022-01-11 Джуно Терапьютикс, Инк. Способы выделения, культивирования и генетической инженерии популяций клеток иммунной системы для адоптивной терапии
ES2839089T3 (es) 2014-05-15 2021-07-05 Nat Univ Singapore Linfocitos citolíticos naturales modificados y usos de los mismos
CN107075483A (zh) 2014-07-15 2017-08-18 朱诺治疗学股份有限公司 用于过继细胞治疗的工程改造的细胞
WO2016014553A1 (fr) 2014-07-21 2016-01-28 Novartis Ag Récepteurs d'antigènes chimères synthétisés par l'intermédiaire d'une sortase
BR112017001183A2 (pt) 2014-07-21 2017-11-28 Novartis Ag tratamento de câncer usando receptor de antígeno quimérico anti-bcma humanizado
KR102594343B1 (ko) 2014-07-21 2023-10-26 노파르티스 아게 Cd33 키메라 항원 수용체를 사용한 암의 치료
SG11201700418VA (en) 2014-07-21 2017-02-27 Novartis Ag Treatment of cancer using a cll-1 chimeric antigen receptor
CN107108744B (zh) 2014-08-19 2020-09-25 诺华股份有限公司 抗cd123嵌合抗原受体(car)用于癌症治疗
TWI805109B (zh) 2014-08-28 2023-06-11 美商奇諾治療有限公司 對cd19具專一性之抗體及嵌合抗原受體
BR112017005390A2 (pt) 2014-09-17 2017-12-12 Novartis Ag células citotóxicas alvo com receptores quiméricos para imunoterapia adotiva
JP6815992B2 (ja) 2014-10-08 2021-01-20 ノバルティス アーゲー キメラ抗原受容体療法に対する治療応答性を予測するバイオマーカーおよびその使用
IL293714A (en) 2014-10-20 2022-08-01 Juno Therapeutics Inc Methods and preparations for dosing in stress cell therapy
PT3215601T (pt) 2014-11-05 2020-08-03 Juno Therapeutics Inc Métodos de transdução e transformação de células
US11266739B2 (en) 2014-12-03 2022-03-08 Juno Therapeutics, Inc. Methods and compositions for adoptive cell therapy
CN107567461A (zh) 2014-12-29 2018-01-09 诺华股份有限公司 制备嵌合抗原受体表达细胞的方法
MA41346A (fr) 2015-01-12 2017-11-21 Juno Therapeutics Inc Eléments régulateurs post-transcriptionnels d'hépatite modifiée
CA2973964A1 (fr) 2015-01-16 2016-07-21 Juno Therapeutics, Inc. Anticorps et recepteurs antigeniques chimeriques specifiques de ror1
WO2016115482A1 (fr) 2015-01-16 2016-07-21 Novartis Pharma Ag Promoteurs de phosphoglycérate kinase 1 (pgk) et procédés d'utilisation pour l'expression d'un récepteur antigénique chimérique
WO2016126608A1 (fr) 2015-02-02 2016-08-11 Novartis Ag Cellules exprimant car dirigées contre de multiples antigènes tumoraux et leurs utilisations
WO2016164731A2 (fr) 2015-04-08 2016-10-13 Novartis Ag Thérapies anti-cd20, thérapies anti-cd22, et polythérapies comprenant une cellule exprimant le récepteur antigénique chimérique (car) dirigé contre le cd19
WO2016166568A1 (fr) 2015-04-16 2016-10-20 Juno Therapeutics Gmbh Procédés, kits et appareil permettant d'augmenter une population de cellules
EP4234685A3 (fr) 2015-04-17 2023-09-06 Novartis AG Procédés pour améliorer l'efficacité et l'expansion de cellules exprimant un récepteur antigénique chimérique
MA43344A (fr) 2015-05-29 2018-04-11 Juno Therapeutics Inc Composition et procédés de régulation des interactions inhibitrices dans les cellules génétiquement modifiées
MA42895A (fr) 2015-07-15 2018-05-23 Juno Therapeutics Inc Cellules modifiées pour thérapie cellulaire adoptive
JP7146632B2 (ja) 2015-07-21 2022-10-04 ノバルティス アーゲー 免疫細胞の有効性および増大を改善する方法
EP3331913A1 (fr) 2015-08-07 2018-06-13 Novartis AG Traitement du cancer à l'aide des protéines de récepteur cd3 chimères
CN108780084B (zh) 2015-09-03 2022-07-22 诺华股份有限公司 预测细胞因子释放综合征的生物标志物
AU2016326738B2 (en) 2015-09-24 2023-08-31 Abvitro Llc HIV antibody compositions and methods of use
WO2017053902A1 (fr) 2015-09-25 2017-03-30 Abvitro Llc Procédé à haut débit pour l'identification ciblée de séquences de récepteurs de lymphocytes t naturellement appariées
MA45489A (fr) 2015-10-22 2018-08-29 Juno Therapeutics Gmbh Procédés de culture de cellules, kits et appareil associés
AU2016341527B2 (en) 2015-10-22 2023-04-27 Juno Therapeutics Gmbh Methods, kits, agents and apparatuses for transduction
MA45488A (fr) 2015-10-22 2018-08-29 Juno Therapeutics Gmbh Procédés, kits et appareil de culture de cellules
WO2017079703A1 (fr) 2015-11-05 2017-05-11 Juno Therapeutics, Inc. Vecteurs et cellules immunitaires génétiquement modifiées exprimant des modulateurs de voie métabolique et utilisations en thérapie cellulaire adoptive
MA44314A (fr) 2015-11-05 2018-09-12 Juno Therapeutics Inc Récepteurs chimériques contenant des domaines induisant traf, et compositions et méthodes associées
MX2018006789A (es) 2015-12-03 2019-02-13 Juno Therapeutics Inc Receptores quimericos modificados y composiciones y metodos relacionados.
US20200297760A1 (en) 2015-12-03 2020-09-24 Juno Therapeutics, Inc. Compositions and methods for reducing immune responses against chimeric antigen receptors
WO2017096331A1 (fr) 2015-12-04 2017-06-08 Juno Therapeutics, Inc. Méthodes et compositions liées à la toxicité associée à la thérapie cellulaire
WO2017112741A1 (fr) 2015-12-22 2017-06-29 Novartis Ag Récepteur d'antigène chimérique (car) contre la mésothéline et anticorps contre l'inhibiteur de pd-l1 pour une utilisation combinée dans une thérapie anticancéreuse
MA43758A (fr) 2016-03-16 2018-11-28 Yuan Ji Procédés pour déterminer le dosage d'un agent thérapeutique et traitements associés
MA43759A (fr) 2016-03-16 2018-11-28 Jason Connor Procédés de conception adaptative d'un régime de traitement et traitements associés
ES2907557T3 (es) 2016-03-22 2022-04-25 Seattle Childrens Hospital Dba Seattle Childrens Res Inst Métodos de intervención temprana para prevenir o mejorar la toxicidad
US11549099B2 (en) 2016-03-23 2023-01-10 Novartis Ag Cell secreted minibodies and uses thereof
IL262772B2 (en) 2016-05-06 2023-10-01 Juno Therapeutics Inc Genetically engineered cells and methods for their preparation
ES2901215T3 (es) 2016-05-27 2022-03-21 Aadigen Llc Péptidos y nanopartículas para la liberación intracelular de moléculas de edición del genoma
EP4011381A1 (fr) 2016-06-03 2022-06-15 Memorial Sloan-Kettering Cancer Center Thérapies cellulaires adoptives utilisées en tant qu'options de traitement précoce
MA45341A (fr) 2016-06-06 2019-04-10 Hutchinson Fred Cancer Res Procédés de traitement de malignités de lymphocytes b au moyen d'une thérapie cellulaire adoptive
CN110291402B (zh) 2016-06-27 2023-09-01 朱诺治疗学股份有限公司 鉴定肽表位的方法、结合此类表位的分子和相关用途
MA45491A (fr) 2016-06-27 2019-05-01 Juno Therapeutics Inc Épitopes à restriction cmh-e, molécules de liaison et procédés et utilisations associés
KR20230107408A (ko) 2016-07-29 2023-07-14 주노 쎄러퓨티크스 인코퍼레이티드 항-cd19 항체에 대한 항-이디오타입 항체
MA45783A (fr) 2016-07-29 2019-06-05 Juno Therapeutics Inc Procédés d'évaluation de la présence ou de l'absence d'un virus compétent pour la réplication
EP3490585B1 (fr) 2016-07-29 2023-05-17 Juno Therapeutics, Inc. Polypeptides immunomdulateurs et compositions et procédés associés
RU2021123536A (ru) 2016-09-12 2022-01-14 Джуно Терапьютикс, Инк. Сборочные узлы перфузионных биореакторных мешков
EP4353319A2 (fr) 2016-09-28 2024-04-17 Atossa Therapeutics, Inc. Procédés de thérapie cellulaire adoptive
CN110139873A (zh) 2016-10-03 2019-08-16 朱诺治疗学股份有限公司 Hpv特异性结合分子
BR112019006781A2 (pt) 2016-10-07 2019-07-30 Novartis Ag receptores de antígeno quiméricos para o tratamento de câncer
US11896615B2 (en) 2016-10-13 2024-02-13 Juno Therapeutics, Inc. Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators
WO2018085731A2 (fr) 2016-11-03 2018-05-11 Juno Therapeutics, Inc. Polythérapie de type thérapie cellulaire t et inhibiteur de btk
MA46716A (fr) 2016-11-03 2019-09-11 Juno Therapeutics Inc Polythérapie de thérapie cellulaire et d'inhibiteur de la microglie
WO2018102786A1 (fr) 2016-12-03 2018-06-07 Juno Therapeutics, Inc. Procédés de modulation de lymphocytes t modifiés par car
AU2017368333A1 (en) 2016-12-03 2019-06-13 Juno Therapeutics, Inc. Methods for determining CAR-T cells dosing
CA3045339A1 (fr) 2016-12-03 2018-06-07 Juno Therapeutics, Inc. Methodes et compositions pour l'utilisation de lymphocytes t therapeutiques en association avec des inhibiteurs de kinase
EP3548611A1 (fr) 2016-12-05 2019-10-09 Juno Therapeutics, Inc. Production de cellules modifiées pour une thérapie cellulaire adoptive
JP7429338B2 (ja) 2017-01-10 2024-02-08 ジュノー セラピューティクス インコーポレイテッド 細胞療法および関連方法のエピジェネティック解析
AU2018209400B2 (en) 2017-01-20 2022-06-02 Juno Therapeutics Gmbh Cell surface conjugates and related cell compositions and methods
US11535662B2 (en) 2017-01-26 2022-12-27 Novartis Ag CD28 compositions and methods for chimeric antigen receptor therapy
IL268349B1 (en) 2017-02-17 2024-04-01 Hutchinson Fred Cancer Res Combination therapies for the treatment of BCMA-associated cancer and autoimmune disorders
KR20200010179A (ko) 2017-02-27 2020-01-30 주노 쎄러퓨티크스 인코퍼레이티드 세포 요법에 있어서 투약과 관련된 조성물, 제조 물품 및 방법
US11850262B2 (en) 2017-02-28 2023-12-26 Purdue Research Foundation Compositions and methods for CAR T cell therapy
EA201992155A1 (ru) 2017-03-14 2020-03-16 Джуно Терапьютикс, Инк. Способы криогенного хранения
EA201992232A1 (ru) 2017-03-22 2020-05-14 Новартис Аг Композиции и способы для иммуноонкологии
CN117363636A (zh) 2017-03-27 2024-01-09 新加坡国立大学 一种编码嵌合受体的多核苷酸
AU2018250336A1 (en) 2017-04-07 2019-09-26 Juno Therapeutics, Inc. Engineered cells expressing prostate-specific membrane antigen (PSMA) or a modified form thereof and related methods
JP7355650B2 (ja) 2017-04-14 2023-10-03 ジュノー セラピューティクス インコーポレイテッド 細胞表面グリコシル化を評価するための方法
WO2018195175A1 (fr) 2017-04-18 2018-10-25 FUJIFILM Cellular Dynamics, Inc. Lymphocytes effecteurs immunitaires spécifiques de l'antigène
CN111032850A (zh) 2017-04-27 2020-04-17 朱诺治疗学有限公司 寡聚粒子试剂及其使用方法
KR20200026805A (ko) 2017-05-01 2020-03-11 주노 쎄러퓨티크스 인코퍼레이티드 세포 요법 및 면역조절 화합물의 조합
CN111201438A (zh) 2017-06-02 2020-05-26 朱诺治疗学股份有限公司 与和细胞疗法相关的毒性有关的制品和方法
CA3065120A1 (fr) 2017-06-02 2018-12-06 Juno Therapeutics, Inc. Articles de fabrication et procedes de traitement utilisant une therapie cellulaire adoptive
LT3538645T (lt) 2017-06-20 2021-04-26 Institut Curie Suv39h1 atžvilgiu defektyvios imuninės ląstelės
AU2018288863A1 (en) 2017-06-22 2020-01-30 Board Of Regents, The University Of Texas System Methods for producing regulatory immune cells and uses thereof
CN111050545A (zh) 2017-06-29 2020-04-21 朱诺治疗学股份有限公司 评估与免疫疗法相关的毒性的小鼠模型
AU2018310452A1 (en) 2017-07-29 2020-02-13 Juno Therapeutics, Inc. Reagents for expanding cells expressing recombinant receptors
MX2020001490A (es) 2017-08-09 2020-08-06 Juno Therapeutics Inc Metodos para producir composiciones de celulas geneticamente modificadas y composiciones relacionadas.
AU2018313952A1 (en) 2017-08-09 2020-02-13 Juno Therapeutics, Inc. Methods and compositions for preparing genetically engineered cells
MA50057A (fr) 2017-09-01 2020-07-08 Juno Therapeutics Inc Expression génique et évaluation d'un risque de développement d'une toxicité suite à une thérapie cellulaire
MA50079A (fr) 2017-09-07 2020-07-15 Juno Therapeutics Inc Procédés d'identification de caractéristiques cellulaires relatives à des réponses associées à une thérapie cellulaire
CN109517820B (zh) 2017-09-20 2021-09-24 北京宇繁生物科技有限公司 一种靶向HPK1的gRNA以及HPK1基因编辑方法
MX2020003536A (es) 2017-10-03 2020-09-14 Juno Therapeutics Inc Moleculas de union especifica a virus de papiloma humano (hpv).
US20210132042A1 (en) 2017-11-01 2021-05-06 Juno Therapeutics, Inc. Methods of assessing or monitoring a response to a cell therapy
AU2018360800A1 (en) 2017-11-01 2020-05-14 Juno Therapeutics, Inc. Chimeric antigen receptors specific for B-cell maturation antigen (BCMA)
SG11202003501XA (en) 2017-11-01 2020-05-28 Juno Therapeutics Inc Antibodies and chimeric antigen receptors specific for b-cell maturation antigen
WO2019089982A1 (fr) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Procédé d'évaluation de l'activité de récepteurs antigéniques de recombinaison
MX2020004239A (es) 2017-11-01 2020-09-09 Juno Therapeutics Inc Proceso para producir una composicion de celulas t.
WO2019089848A1 (fr) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Procédés associés à une charge tumorale pour évaluer une réponse à une thérapie cellulaire
BR112020008478A2 (pt) 2017-11-01 2020-10-20 Editas Medicine, Inc. métodos, composições e componentes para edição de crispr-cas9 de tgfbr2 em células t para imunota-rapia
CN111542596A (zh) 2017-11-01 2020-08-14 朱诺治疗学股份有限公司 产生工程化细胞的治疗性组合物的方法
JP2021502077A (ja) 2017-11-06 2021-01-28 エディタス・メディシン，インコーポレイテッド 免疫療法のためのｔ細胞におけるｃｂｌｂのｃｒｉｓｐｒ−ｃａｓ９編集のための方法、組成物および構成要素
EP3706754A1 (fr) 2017-11-06 2020-09-16 Juno Therapeutics, Inc. Association d'une thérapie cellulaire et d'un inhibiteur de gamma secrétase
EP3706904A1 (fr) 2017-11-10 2020-09-16 Juno Therapeutics, Inc. Réservoirs cryogéniques à système fermé
KR20200116081A (ko) 2017-12-01 2020-10-08 주노 쎄러퓨티크스 인코퍼레이티드 유전자 조작된 세포의 투약 및 조절 방법
CN112203680A (zh) 2017-12-08 2021-01-08 朱诺治疗学股份有限公司 用于细胞疗法的表型标记和相关方法
CN112041430A (zh) 2017-12-08 2020-12-04 朱诺治疗学股份有限公司 用于培养细胞的无血清培养基配制品及其使用方法
MX2020005908A (es) 2017-12-08 2020-10-07 Juno Therapeutics Inc Proceso para producir una composicion de celulas t modificadas.
MA51184A (fr) 2017-12-15 2020-10-21 Juno Therapeutics Inc Molécules de liaison à l'anti-cct5 et procédés d'utilisation associés
WO2019139972A1 (fr) 2018-01-09 2019-07-18 Board Of Regents, The University Of Texas System Récepteurs de lymphocytes t pour l'immunothérapie
JP2021512147A (ja) 2018-01-22 2021-05-13 エンドサイト・インコーポレイテッドＥｎｄｏｃｙｔｅ， Ｉｎｃ． Ｃａｒ ｔ細胞の使用方法
JP2021511802A (ja) 2018-01-31 2021-05-13 ジュノー セラピューティクス インコーポレイテッド 複製可能ウイルスの存在または非存在を評価するための方法および試薬
US20210069246A1 (en) 2018-01-31 2021-03-11 Celgene Corporation Combination therapy using adoptive cell therapy and checkpoint inhibitor
JP2021514658A (ja) 2018-03-06 2021-06-17 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア 前立腺特異的膜抗原ｃａｒおよびその使用方法
WO2019170845A1 (fr) 2018-03-09 2019-09-12 Ospedale San Raffaele S.R.L. Antagoniste de l'il-1 et toxicité induite par la thérapie cellulaire
SG11202009284TA (en) 2018-04-05 2020-10-29 Juno Therapeutics Inc T cell receptors and engineered cells expressing same
KR20210029707A (ko) 2018-04-05 2021-03-16 주노 쎄러퓨티크스 인코퍼레이티드 재조합 수용체를 발현하는 세포의 생산 방법 및 관련 조성물
KR20210044736A (ko) 2018-05-03 2021-04-23 주노 쎄러퓨티크스 인코퍼레이티드 키메라 항원 수용체(ｃａｒ) ｔ세포 요법과 키나제 억제제의 조합요법
BR112020025048A2 (pt) 2018-06-13 2021-04-06 Novartis Ag Receptores de antígeno quimérico de bcma e usos dos mesmos
KR20210057730A (ko) 2018-08-09 2021-05-21 주노 쎄러퓨티크스 인코퍼레이티드 조작 세포 및 이의 조성물 생성 방법
SG11202101130VA (en) 2018-08-09 2021-03-30 Juno Therapeutics Inc Methods for assessing integrated nucleic acids
CA3110089A1 (fr) 2018-08-28 2020-03-05 Fred Hutchinson Cancer Research Center Procedes et compositions pour therapie adoptive par lymphocytes t comportant une signalisation notch induite
US20220050114A1 (en) 2018-09-11 2022-02-17 Juno Therapeutics, Inc. Methods for mass spectrometry analysis of engineered cell compositions
CN113227358A (zh) 2018-10-31 2021-08-06 朱诺治疗学有限公司 选择并刺激细胞的方法及用于所述方法的设备
CN113646335A (zh) 2018-11-01 2021-11-12 朱诺治疗学股份有限公司 使用对b细胞成熟抗原具有特异性的嵌合抗原受体的治疗的方法
CA3117720A1 (fr) 2018-11-06 2020-05-14 Juno Therapeutics, Inc. Procede de production de cellules t genetiquement modifiees
CA3117978A1 (fr) 2018-11-08 2020-05-14 Juno Therapeutics, Inc. Procedes et combinaisons pour le traitement et la modulation de lymphocytes t
MX2021005734A (es) 2018-11-16 2021-09-10 Juno Therapeutics Inc Metodos de dosificacion de celulas t modificadas para el tratamiento de malignidades de celulas b.
CN113286813A (zh) 2018-11-19 2021-08-20 得克萨斯大学体系董事会 用于car和tcr转导的模块化多顺反子载体
JP2022513652A (ja) 2018-11-28 2022-02-09 ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム 機能および抑制性環境に対する抵抗性を増強するための免疫細胞のマルチプレックスゲノム編集
US20220033778A1 (en) 2018-11-29 2022-02-03 Board Of Regents, The University Of Texas System Methods for ex vivo expansion of natural killer cells and use thereof
JP2022513685A (ja) 2018-11-30 2022-02-09 ジュノー セラピューティクス インコーポレイテッド 養子細胞療法を用いた処置のための方法
AU2019387494A1 (en) 2018-11-30 2021-06-10 Juno Therapeutics, Inc. Methods for dosing and treatment of B cell malignancies in adoptive cell therapy
US20220096651A1 (en) 2019-01-29 2022-03-31 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for receptor tyrosine kinase like orphan receptor 1 (ror1)
CA3131533A1 (fr) 2019-03-05 2020-09-10 Nkarta, Inc. Recepteurs d'antigenes chimeriques anti-cd19 et leurs utilisations en immunotherapie
US20220218750A1 (en) 2019-05-01 2022-07-14 Juno Therapeutics, Inc. Cells expressing a chimeric receptor from a modified cd247 locus, related polynucleotides and methods
KR20220016475A (ko) 2019-05-01 2022-02-09 주노 쎄러퓨티크스 인코퍼레이티드 변형된 ｔｇｆｂｒ2 유전자 좌에서 재조합 수용체를 발현하는 세포, 관련 폴리뉴클레오티드 및 방법
US20220228101A1 (en) 2019-06-07 2022-07-21 Juno Therapeutics, Inc. Automated t cell culture
CA3142361A1 (fr) 2019-06-12 2020-12-17 Juno Therapeutics, Inc. Combinaison therapeutique d'une therapie cytotoxique a mediation cellulaire et d'un inhibiteur d'une proteine de la famille bcl2 pro-survie
BR112022001148A2 (pt) 2019-07-23 2022-03-15 Inst Nat Sante Rech Med Células imunes modificadas, composição farmacêutica, kit, uso de uma célula imune modificada e invenção de produto
WO2021035194A1 (fr) 2019-08-22 2021-02-25 Juno Therapeutics, Inc. Polythérapie basée sur une thérapie par lymphocytes t et un inhibiteur de protéine-2 homologue de l'activateur de zeste (ezh2) et procédés associés
WO2021041994A2 (fr) 2019-08-30 2021-03-04 Juno Therapeutics, Inc. Procédés d'apprentissage automatique pour la classification de cellules
CA3158775A1 (fr) 2019-09-02 2021-03-11 Institut Curie Immunotherapie ciblant des peptides neoantigeniques tumoraux
EP4048304A1 (fr) 2019-10-22 2022-08-31 Institut Curie Immunothérapie ciblant des peptides néo-antigéniques tumoraux
JP2023500318A (ja) 2019-10-30 2023-01-05 ジュノ セラピューティクス ゲーエムベーハー 細胞選択および／または細胞刺激デバイスならびに使用方法
US20220401483A1 (en) 2019-11-07 2022-12-22 Juno Therapeutics, Inc. Combination of a t cell therapy and (s)-3-[4-(4-morpholin-4-ylmethyl-benzyloxy)-l-oxo-l,3-dihydro-isoindol-2-yl]-piperidine-2,6-dione
JP2023504740A (ja) 2019-12-06 2023-02-06 ジュノー セラピューティクス インコーポレイテッド Ｂｃｍａ標的結合ドメインに対する抗イディオタイプ抗体ならびに関連する組成物および方法
WO2021113780A1 (fr) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Anticorps anti-idiotypiques dirigés contre des domaines de liaison ciblant gprc5d et compositions et procédés associés
WO2021113770A1 (fr) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Procédés liés à la toxicité et à la réponse associées à une thérapie cellulaire pour le traitement de tumeurs malignes des lymphocytes b
EP4093433A1 (fr) 2020-01-24 2022-11-30 Juno Therapeutics, Inc. Méthodes de dosage et de traitement de lymphome folliculaire et de lymphome de la zone marginale en thérapie cellulaire adoptive
US20230090117A1 (en) 2020-01-28 2023-03-23 Juno Therapeutics, Inc. Methods for t cell transduction
EP4103203A1 (fr) 2020-02-12 2022-12-21 Juno Therapeutics, Inc. Compositions de lymphocytes t à récepteur antigénique chimérique contre bcma et procédés et utilisations associés
JP2023519098A (ja) 2020-02-12 2023-05-10 ジュノー セラピューティクス インコーポレイテッド Ｃｄ１９指向性キメラ抗原受容体ｔ細胞組成物ならびにその方法および使用
CA3168337A1 (fr) 2020-02-17 2021-08-26 Marie-Andree Forget Procedes d'expansion de lymphocytes infiltrant les tumeurs et leur utilisation
WO2021207689A2 (fr) 2020-04-10 2021-10-14 Juno Therapeutics, Inc. Méthodes et utilisations associées à une thérapie cellulaire modifiée à l'aide d'un récepteur antigénique chimérique ciblant un antigène de maturation des lymphocytes b
US20230212243A1 (en) 2020-05-12 2023-07-06 Institut Curie Neoantigenic Epitopes Associated with SF3B1 Mutations
CN115803824A (zh) 2020-05-13 2023-03-14 朱诺治疗学股份有限公司 鉴定与临床反应相关的特征的方法及其用途
EP4150057A2 (fr) 2020-05-13 2023-03-22 Juno Therapeutics, Inc. Procédé de production de lots de cellules donneuses exprimant un récepteur recombinant
CA3178726A1 (fr) 2020-05-21 2021-11-25 Gregory LIZEE Recepteurs de lymphocytes t ayant une specificite pour le vgll1 et leurs utilisations
JP2023531531A (ja) 2020-06-26 2023-07-24 ジュノ セラピューティクス ゲーエムベーハー 組換え受容体を条件付きで発現する操作されたｔ細胞、関連ポリヌクレオチド、および方法
CA3190266A1 (fr) 2020-07-30 2022-02-03 Institut Curie Cellules immunitaires defectives en socs1
KR20230095918A (ko) 2020-08-05 2023-06-29 주노 쎄러퓨티크스 인코퍼레이티드 Ror1-표적 결합 도메인에 대한 항이디오타입 항체 및 관련 조성물 및 방법
US20230051406A1 (en) 2020-11-13 2023-02-16 Catamaran Bio, Inc. Genetically modified natural killer cells and methods of use thereof
WO2022133030A1 (fr) 2020-12-16 2022-06-23 Juno Therapeutics, Inc. Polythérapie de thérapie cellulaire et d'inhibiteur de bcl2
WO2022150731A1 (fr) 2021-01-11 2022-07-14 Sana Biotechnology, Inc. Utilisation de vecteurs viraux ciblant cd8
WO2022187406A1 (fr) 2021-03-03 2022-09-09 Juno Therapeutics, Inc. Combinaison d'une thérapie par lymphocytes t et d'un inhibiteur de dgk
AU2022233019A1 (en) 2021-03-11 2023-09-28 INSERM (Institut National de la Santé et de la Recherche Médicale) Tumor neoantigenic peptides
CA3213004A1 (fr) 2021-03-11 2022-09-15 Mnemo Therapeutics Peptides neo-antigeniques tumoraux et leurs utilisations
KR20240006721A (ko) 2021-03-11 2024-01-15 엥스띠뛰 퀴리 막 형질 전환 네오 안티젠 펩타이드
KR20230159851A (ko) 2021-03-22 2023-11-22 주노 쎄러퓨티크스 인코퍼레이티드 치료 세포 조성물의 효력을 결정하는 방법
CN117321200A (zh) 2021-03-22 2023-12-29 朱诺治疗学股份有限公司 评估病毒载体颗粒效力的方法
EP4313127A1 (fr) 2021-03-29 2024-02-07 Juno Therapeutics, Inc. Méthodes de dosage et de traitement au moyen d'une combinaison d'une thérapie par inhibiteur de point de contrôle et d'une thérapie par lymphocytes car t
AU2022252220A1 (en) 2021-03-29 2023-10-12 Juno Therapeutics, Inc. Combination of a car t cell therapy and an immunomodulatory compound for treatment of lymphoma
EP4334341A2 (fr) 2021-05-06 2024-03-13 Juno Therapeutics GmbH Méthodes de stimulation et de transduction de lymphocytes t
WO2023015217A1 (fr) 2021-08-04 2023-02-09 Sana Biotechnology, Inc. Utilisation de vecteurs viraux ciblant cd4
WO2023014922A1 (fr) 2021-08-04 2023-02-09 The Regents Of The University Of Colorado, A Body Corporate Cellules t de récepteur d'antigène chimérique activant le lat et leurs méthodes d'utilisation
WO2023105000A1 (fr) 2021-12-09 2023-06-15 Zygosity Limited Vecteur
WO2023115039A2 (fr) 2021-12-17 2023-06-22 Sana Biotechnology, Inc. Glycoprotéines de fusion de paramyxoviridae modifiées
TW202342757A (zh) 2021-12-17 2023-11-01 美商薩那生物科技公司 經修飾副黏液病毒科附著醣蛋白
WO2023126458A1 (fr) 2021-12-28 2023-07-06 Mnemo Therapeutics Cellules immunitaires avec suv39h1 inactivé et tcr modifié
WO2023139269A1 (fr) 2022-01-21 2023-07-27 Mnemo Therapeutics Modulation de l'expression de suv39h1 par arn
WO2023147515A1 (fr) 2022-01-28 2023-08-03 Juno Therapeutics, Inc. Procédés de fabrication de compositions cellulaires
WO2023150518A1 (fr) 2022-02-01 2023-08-10 Sana Biotechnology, Inc. Vecteurs lentiviraux ciblant cd3 et leurs utilisations
WO2023178348A1 (fr) 2022-03-18 2023-09-21 The Regents Of The University Of Colorado, A Body Corporate Co-récepteurs de lymphocytes t génétiquement modifiés et leurs procédés d'utilisation
WO2023180552A1 (fr) 2022-03-24 2023-09-28 Institut Curie Immunothérapie ciblant des peptides néoantigéniques dérivés d'un élément transposable spécifique d'une tumeur dans un glioblastome
WO2023193015A1 (fr) 2022-04-01 2023-10-05 Sana Biotechnology, Inc. Polythérapies d'agoniste de récepteur de cytokine et de vecteur viral
WO2023196921A1 (fr) 2022-04-06 2023-10-12 The Regents Of The University Of Colorado, A Body Corporate Lymphocytes t exprimant la granzyme et méthodes d'utilisation
WO2023196933A1 (fr) 2022-04-06 2023-10-12 The Regents Of The University Of Colorado, A Body Corporate Lymphocytes t à récepteurs antigéniques chimériques et leurs procédés d'utilisation
WO2023211972A1 (fr) 2022-04-28 2023-11-02 Medical University Of South Carolina Lymphocytes t régulateurs modifiés par un récepteur antigénique chimérique pour le traitement du cancer
WO2023213969A1 (fr) 2022-05-05 2023-11-09 Juno Therapeutics Gmbh Protéine de liaison virale et réactifs, articles et méthodes d'utilisation associés
WO2023220655A1 (fr) 2022-05-11 2023-11-16 Celgene Corporation Méthodes pour surmonter la résistance aux médicaments par ré-sensibilisation de cellules cancéreuses à un traitement avec une thérapie antérieure par l'intermédiaire d'un traitement avec une thérapie par lymphocytes t
EP4279085A1 (fr) 2022-05-20 2023-11-22 Mnemo Therapeutics Compositions et procédés de traitement d'un cancer réfractaire ou récurrent ou d'une maladie infectieuse chronique
WO2023230581A1 (fr) 2022-05-25 2023-11-30 Celgene Corporation Procédés de fabrication de thérapies par lymphocytes t
WO2023250400A1 (fr) 2022-06-22 2023-12-28 Juno Therapeutics, Inc. Méthodes de traitement pour thérapie de deuxième ligne par cellules car-t ciblées par cd19
WO2024006960A1 (fr) 2022-06-29 2024-01-04 Juno Therapeutics, Inc. Nanoparticules lipidiques pour l'administration d'acides nucléiques
WO2024044779A2 (fr) 2022-08-26 2024-02-29 Juno Therapeutics, Inc. Anticorps et récepteurs antigéniques chimériques spécifiques d'un ligand 3 de type delta (dll3)
WO2024054944A1 (fr) 2022-09-08 2024-03-14 Juno Therapeutics, Inc. Combinaison de thérapie cellulaire t et de dosage continu ou intermittent d'inhibiteurs de dgk
WO2024062138A1 (fr) 2022-09-23 2024-03-28 Mnemo Therapeutics Cellules immunitaires comprenant un gène suv39h1 modifié
WO2024081820A1 (fr) 2022-10-13 2024-04-18 Sana Biotechnology, Inc. Particules virales ciblant des cellules souches hématopoïétiques

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5891680A (en) * 1995-02-08 1999-04-06 Whitehead Institute For Biomedical Research Bioactive fusion proteins comprising the p35 and p40 subunits of IL-12

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ALVAREZ-VALLINA L ET AL: "ANTIGEN-SPECIFIC TARGETING OF CD28-MEDIATED T CELL CO-STIMULATION USING CHIMERIC SINGLE-CHAIN ANTIBODY VARIABLE FRAGMENT-CD28 RECEPTORS" EUROPEAN JOURNAL OF IMMUNOLOGY, WEINHEIM, DE, vol. 26, no. 10, 1 October 1996 (1996-10-01), pages 2304-2309, XP000646504 ISSN: 0014-2980 *
MORITZ D ET AL: "A SPACER REGION BETWEEN THE SINGLE CHAIN ANTIBODY AND THE CD3 KSI-CHAIN DOMAIN OF CHIMERIC T CELL RECEPTOR COMPONENTS IS REQUIRED FOR EFFICIENT LIGAND BINDING AND SIGNALING ACTIVITY" GENE THERAPY, MACMILLAN PRESS LTD., BASINGSTOKE, GB, vol. 2, no. 8, 1 October 1995 (1995-10-01), pages 539-546, XP000674790 ISSN: 0969-7128 *
See also references of WO0014257A1 *
TRAN A-C ET AL: "CHIMERIC DZETA-RECEPTORS DIRECT HUMAN NATURAL KILLER (NK) EFFECTOR FUNCTION TO PERMIT KILLING OF NK-RESISTANT TUMOR CELLS AND HIV-INFECTED T LYMPHOCYTES" JOURNAL OF IMMUNOLOGY, THE WILLIAMS AND WILKINS CO. BALTIMORE, US, vol. 155, no. 2, June 1995 (1995-06), pages 1000-1009, XP000882943 ISSN: 0022-1767 *

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