WO2005005623A1 - Procede de lyse de cellules tumorales - Google Patents

Procede de lyse de cellules tumorales Download PDF

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Publication number
WO2005005623A1
WO2005005623A1 PCT/KZ2004/000001 KZ2004000001W WO2005005623A1 WO 2005005623 A1 WO2005005623 A1 WO 2005005623A1 KZ 2004000001 W KZ2004000001 W KZ 2004000001W WO 2005005623 A1 WO2005005623 A1 WO 2005005623A1
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WO
WIPO (PCT)
Prior art keywords
cells
antibodies
fetoprotein
antiidiotypical
lysis
Prior art date
Application number
PCT/KZ2004/000001
Other languages
English (en)
Inventor
Alexandr Frantsev
Irina Frantseva
Yelena Medvedeva
Original Assignee
Real Med Company Limited
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 Real Med Company Limited filed Critical Real Med Company Limited
Publication of WO2005005623A1 publication Critical patent/WO2005005623A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07K16/3076—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 against structure-related tumour-associated moieties
    • 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

Definitions

  • This invention relates to immunology and may be used in different fields of medicine and veterinary.
  • Resent ways of influence on modified cells are not selective enough and they are harmful for both: bad cells causing illness and for healthy ones.
  • Ethoposid has a special feature enabling him to stop cells cycle on G2 stage.
  • "Vepezid” suppresses timidine's involvement in to the DNA. Its high concentrations lead to the mitosis cells lysis.Vepezid is effective against the number of animal tumors and also for some of human tumors including: small cells bronchus carcinoma, malignant lymphogranulomatosis and malignant lymphoma advanced stages, acute recured not lymphocytic leucaemia, ovarian seminoma.
  • Antibodies are fixed by the steady domain to the Fc receptor's cytotoxic lymphocyte, and with hyper variable domain to proper antigen.
  • Monoclonal antibody's antineoplastic operation mechanism in rather difficult and includes the following components: - Alexine-dependant cytotoxicity; - Antibody-dependant cell's cytotoxicity; - Ab2 vaccines; - Phagocytosis (activated microphages only); - Receptors bloke (antireceptors); - Apoptosis,; - Intracellular effects The most significant are first three mechanisms. During the alexine- dependant cytotoxicity realization there is staged alexine system energization on the tumor cells surface.
  • C9 protein forms on the last stage and it is able to form a foramenin in cell's basal membrane that leads to the cell's death.
  • Second important mechanism is antibody-dependant cytotoxicity. During this process monoclonal antibody gets involved with proper antigen on the tumor cell surface using its hyper variable domain. The same way antibody's constant gene contacts cytotoxic lymphocyte's Fc-receptors, so-called "killers". The latter ones are capable of synthesizing and protein output and serine protease injuring cell's membrane. This protein (perform) is equal to C9 alexine system.
  • Third important antineoplastic mechanism of monoclonal antibodies is so- called Ab2 vaccine mechanism.
  • modified cell's lysis method providing lysis high effectiveness and side effects correction.
  • modified cells lysis method including influence of of antiidiotypical antibodies in vivo and in vitro according to the invention the influence is carried out to antiidiotypical antibodies to ⁇ - fetoprotein of a man and animals.
  • ⁇ -fetoprotein- glycoprotein with molecular mass 69 000 consisting of one polypeptide chain, including ⁇ 600 amino acids and containing about 4% of carbohydrates.
  • SA accomplishes transportation of low-molecular substances in tissues.
  • A-fetoprotein serves as a substitute for SA for embryos, frequently called embryonal SA's, and its function is most likely the same - transportation.
  • A-fetoprotein has exceptional affinity to the polyunsaturated fatty acids, substances essential for cell's membrane construction and special class of biologically active substance - prostaglandins. Most probable function of a-fetoprotein is selective connection of polyunsaturated fatty acids in placenta and their transportation from mother's blob to the embryo's blood and tissues. Polyunsaturated fatty acids are synthesized neither by embryo nor by adult and delivered in organism only by vegetal food.
  • the activators tissues (blood) structure G + or G- bacteria, immune complexes) activation of the system occurs it is the cascade interaction of protein system alexine to formation of intermediate products, with the formation of damages in a membrane of targets cells, neutralization of viruses.
  • the system includes more than 25 proteins, nine of them are alexine proteins (CI -C9), and others are (B, D, P, H etc.) factors.
  • alexine proteins CI -C9
  • the fragment C4b intermixes with protein C2, the formed complex C4b2 becomes substratum for Clqrs, a fragment C2b rifts from it, and formed complex C4b2a catalyzes disintegration C3 on the fragments. Sequence of events occurring after splitting C3.
  • the objective of the following stage is the formation of the membrane attacking complex (MAC), which consists of protein C5 - C9 and 80-90 % similar to perform.
  • MAC membrane attacking complex
  • C5 protein joins to the fragment fixed on a membrane of a cell C3b. From the formed complex C3b5 under C3bB5 influence rifts C5a, and proteins C6, C7, C8 consistently join C3b5b.
  • the culmination of the given process is C9 connection, after that a change of all conformation complex appears and funnel-shaped aperture is formed in a membrane as a result cell's lysis sets in.
  • the essence of the offered invention on the use of antiidiotypical antibodies for selective, including alexine - dependent lysis of cells distinguished on histomorphological attributes from normal cells consists in introduction into recipient 's organism of antiidiotypical antibodies to ⁇ - fetoprotein of a man or animals, and the components alexine available in blood and physiological liquids of the recipient's organism participate in the realization alexine - dependent lysis of the changed target cells and within the use of antiidiotypical antibodies to ⁇ - fetoprotein externally, for impregnation of mucous tissue and the recipient's skin, in addition to antiidiotypical antibodies to ⁇ - fetoprotein add alexine components which is necessary in this case.
  • antiiidiotypical antibodies to ⁇ - fetoprotein show affinity with only special morphological structures on a surface of the changed cells and do not show specificity to the structures of the normal not changed cellular surfaces of the man and animals cells tissues.
  • Offered use of antiidiotypical antibodies to ⁇ - fetoprotein of a man and animals allows to carry out in vivo and in vitro selective, alexine -dependent lysis of cells distinguished on histomorphological attributes from normal cells, including tumors without influence on the other, normal organism cells. They receive antiidiotypical antibodies to ⁇ - fetoprotein within the known methods, for example, spirits fractionating of protein blood serum by Conn's method (Conn E. J. 1950), after preliminary man either animals' immunization cellular receptors or antibodies to genetic engineering or natural ⁇ - fetoprotein.
  • BRIEF DESCRIPTION OF DRAWINGS BRIEF DESCRIPTION OF DRAWINGS
  • the invention is elucidated by the photos, where on fig. 1 neoplasm is shown its size is 1,5 x 0,9 x 0,8 cm, protruding above a skin level patient's neck of the and vascular formation the size is 0,6 x 0,7 cm on a breast at the left nipple; on the fig. 2 - 5 dynamic process of neoplasmon destruction on the patient's skin during the current term it's is equal to four weeks and submitted period between each snapshot performance makes one week; on the fig.
  • Example 1 The MODES FOR CARRING OUT THE INVENTION Use of antiidiotypical antibodies to ⁇ - fetoprotein for selective, alexine - dependent lysis of the cells distinguished on histomorphological attributes from normal cells of organism as follows.
  • Example 1 The patient G., age 56 years old, (out-patient card N_> 5117006), patient of polyclinic MIA Almaty is registered on the account at oncologist.
  • the patient had a rontgenotherapy concerning basiloma of a right sided forehead skin.
  • neoplasm located on a skin, and in area of the left nipple of the patient G. used a mixture of equal quantities of antiidiotypical antibodies to ⁇ - fetoprotein and complete set of alexme components.
  • small gauze tampon were impregnated which were imposed directly on neoplasm in area of a neck and nipples, the tampon were covered by a polyethylene for drying speed decreasing, were fixed with the help of court plaster and remained on a body for 2 hours.
  • the specified procedure was carried out two times per day within one month. During the specified period of time there was a destruction of neoplasm on a neck of the patient G.
  • animals hypodermic inoculation of exogenous, "ready” antiidiotypical antibodies to ⁇ - fetoprotein results to lysis of changed tumors cells.
  • the research work under the studding of an induction possibility in rats' organism inoculated with ascites tumor of ovaries, with own antiidiotypical antibodies to ⁇ - fetoprotein , according to the "vaccination” principle was carried out with the use of cleared she goats antibodies to ⁇ - fetoprotein.
  • intra-abdominaly inoculated a sterile solution of she goats antibodies to ⁇ - fetoprotein of the man.
  • Example 3 The researches of cytolytic activity of mixture from antiidiotypical antibodies to ⁇ - fetoprotein and alexine components in vitro were carried out on eleven kinds of shortly living cell cultures, their number included peripheral blood cells of five leucosis patients, the cells of reinoculation of mice Erlih's tumor, ascites tumor of ovaries, psoriasis and anemia patients' blood. As the control, in all cases we used the peripheral blood cells of the healthy people or homologous animals. Samples of blood cells were mixed with quintuple volume quantity of nutritious medium 199, and added a mixture of equal quantities of antiidiotypical antibodies to ⁇ - fetoprotein and alexine components. Incubation of cells preparations was carried out in CO2 incubator, at 36 ° C.
  • peripheral blood which morphological structure varies from influence on them antiidiotypical antibodies to ⁇ - fetoprotein and alexme components, can serve a diagnostic indication of presence in researched organism serious system abnormality.
  • the results of cells incubation of leucosis patients peripheral blood are shown on fig. 10 - 15.
  • Antiidiotypical antibodies to ⁇ - fetoprotein as an independent product or in a combination with alexine components allows to carry out in vitro and in vivo selective lysis of changed cells of a man and animals tissues , having structures on surface of cells walls distinguishing them from usual organism cells that can be used with the diagnostics, prophylaxis purposes, treatment of diseases, and also for application in scientific experiments.
  • the complete absence of the negative phenomena from influence of the declared preparation such as rhematolytic toxicity (leukopenia, thrombopenia), gastrointestinal toxicity (diarrhea, nausea, vomiting), anorexia, anaphylactic reaction is experimentally confirmed.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Endocrinology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne l'immunologie et peut présenter des applications dans divers domaines de la médecine et de la médecine vétérinaire. L'invention a trait à un procédé de lyse des cellules modifiées comprenant l'application de l'influence d'anticorps anti-idiotypes sur elles in vivo et in vitro, ainsi cette influence est réalisée par des anticorps anti-idiotypes vers l'α-fétoprotéine de l'homme ou des animaux.
PCT/KZ2004/000001 2003-07-11 2004-03-11 Procede de lyse de cellules tumorales WO2005005623A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KZ2003/0981.1 2003-07-11
KZ20030981 2003-07-11

Publications (1)

Publication Number Publication Date
WO2005005623A1 true WO2005005623A1 (fr) 2005-01-20

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EA (1) EA200400144A1 (fr)
WO (1) WO2005005623A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7794968B2 (en) 2003-07-10 2010-09-14 Ben-Gurion University Of The Negev Research And Development Authority Polydiacetylene-containing solid colorimetric and/or fluorescent detector, method for its preparation and uses thereof

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
CULL G ET AL: "Generation of anti-idiotype immune responses following vaccination with idiotype-protein pulsed dendritic cells in myeloma", BRITISH JOURNAL OF HAEMATOLOGY, vol. 107, no. 3, December 1999 (1999-12-01), pages 648 - 655, XP002286726, ISSN: 0007-1048 *
DURRANT L G ET AL: "ANTI-IDIOTYPIC VACCINATION", CANCER IMMUNOLOGY, vol. 30, 2001, IMMUNOLOGY AND MEDICINE SERIES, MTP PRESS, LANCASTER, GB, pages 171 - 180, XP008030329, ISSN: 1359-6306 *
FRANKI SUZANNE N ET AL: "Dendritic cells co-cultured with antibody-coated tumor cells provide protective immunity against B cell lymphoma in vivo.", BLOOD, vol. 102, no. 11, 16 November 2003 (2003-11-16), & 45TH ANNUAL MEETING OF THE AMERICAN SOCIETY OF HEMATOLOGY; SAN DIEGO, CA, USA; DECEMBER 06-09, 2003, pages 107a, XP001196973, ISSN: 0006-4971 *
HERLYN D ET AL: "INDUCTION OF SPECIFIC IMMUNITY TO HUMAN COLON CARCINOMA BY ANTI-IDIOTYPIC ANTIBODIES TO MONOCLONAL ANTIBODY CO17-1A", EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 17, no. 11, 1987, pages 1649 - 1652, XP008032412, ISSN: 0014-2980 *
MIZEJEWSKI GERALD J: "Biological role of alpha-fetoprotein in cancer: prospects for anticancer therapy.", EXPERT REVIEW OF ANTICANCER THERAPY. DEC 2002, vol. 2, no. 6, December 2002 (2002-12-01), pages 709 - 735, XP001197359, ISSN: 1473-7140 *
REINARTZ SILKE ET AL: "Immunological properties of a single-chain fragment of the anti-idiotypic antibody ACA125", CANCER IMMUNOLOGY IMMUNOTHERAPY, vol. 49, no. 4-5, July 2000 (2000-07-01), pages 186 - 192, XP002286724, ISSN: 0340-7004 *
SCHLUEP M ET AL: "A SYNGENEIC MONOCLONAL ANTI-IDIOTYPE ANTIBODY AGAINST HNK-1: CHARACTERIZATION AND CYTOTOXIC ACTIVITY IN VITRO", CLINICAL AND EXPERIMENTAL IMMUNOLOGY, OXFORD, GB, vol. 75, no. 2, 1989, pages 301 - 305, XP008032413, ISSN: 0009-9104 *
WILKINSON R W ET AL: "A transgenic mouse model for tumour immunotherapy: Induction of an anti-idiotype response to human MUC1", BRITISH JOURNAL OF CANCER, vol. 83, no. 9, November 2000 (2000-11-01), pages 1202 - 1208, XP002286725, ISSN: 0007-0920 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7794968B2 (en) 2003-07-10 2010-09-14 Ben-Gurion University Of The Negev Research And Development Authority Polydiacetylene-containing solid colorimetric and/or fluorescent detector, method for its preparation and uses thereof

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EA004717B1 (ru) 2004-06-24
EA200400144A1 (ru) 2004-06-24

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