WO1997026910A2 - Vaccin antitumoral pour le traitement immunitaire des tumeurs malignes - Google Patents

Vaccin antitumoral pour le traitement immunitaire des tumeurs malignes Download PDF

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Publication number
WO1997026910A2
WO1997026910A2 PCT/DE1997/000172 DE9700172W WO9726910A2 WO 1997026910 A2 WO1997026910 A2 WO 1997026910A2 DE 9700172 W DE9700172 W DE 9700172W WO 9726910 A2 WO9726910 A2 WO 9726910A2
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WO
WIPO (PCT)
Prior art keywords
tumor
vaccine according
heat shock
shock protein
protein
Prior art date
Application number
PCT/DE1997/000172
Other languages
German (de)
English (en)
Other versions
WO1997026910A3 (fr
Inventor
Jürgen MILLECK
Werner Reichardt
Rainer Benndorf
Windfried Liebrich
Peter Schlag
Original Assignee
Max-Delbrück-Centrum für Molekulare Medizin
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
Priority claimed from DE19602985A external-priority patent/DE19602985A1/de
Priority claimed from DE19604380A external-priority patent/DE19604380A1/de
Application filed by Max-Delbrück-Centrum für Molekulare Medizin filed Critical Max-Delbrück-Centrum für Molekulare Medizin
Publication of WO1997026910A2 publication Critical patent/WO1997026910A2/fr
Publication of WO1997026910A3 publication Critical patent/WO1997026910A3/fr

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Classifications

    • 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
    • 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
    • A61K39/0005—Vertebrate antigens
    • A61K39/0011—Cancer antigens
    • A61K39/001169—Tumor associated carbohydrates
    • A61K39/00117—Mucins, e.g. MUC-1
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5152—Tumor cells
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5156—Animal cells expressing foreign proteins
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55516—Proteins; Peptides
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55588—Adjuvants of undefined constitution
    • A61K2039/55594—Adjuvants of undefined constitution from bacteria
    • 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
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6043—Heat shock proteins

Definitions

  • the invention relates to the production of a vaccine from genetically modified tumor cells or from biochemically isolated tumor-associated antigens or synthetically produced antigenic substructures for the immunotherapy of malignant tumors. Areas of application of the invention are medicine and the pharmaceutical industry.
  • the basic therapy for solid malignant tumors is the surgical or radiotherapy removal of the primary tumor.
  • chemotherapy is carried out or biological therapy is attempted.
  • the generation of an immune response directed against cancer cells which leads to the destruction of the cancer cells, but which does not disturb the healthy tissue, is the optimal method for combating tumor metastases.
  • the fact that it is possible in principle to generate an immune response directed against cancer cells is demonstrated by the results of vaccination experiments with animal experimental tumors and also with some human tumors.
  • tumor cell vaccines In order to elicit an effective immunological defense reaction against malignant tumors, it is essential to artificially increase the immunogenicity of those tumor cells or tumor-associated antigens with which one wants to vaccinate.
  • this can be done by externally modifying the tumor cells chemically, enzymatically or by adding apathogenic viruses or weakened tubercle bacteria (BCG) or by genetic engineering by transmission e.g. a cytokingens changed (Specific Immunotherapy of Can cer with Vaccines, eds. Bystryn et al., Ann NY Acad Sei 690 (1993); Pardoll, Curr Opin Immunol 4, 619-623 (1992)).
  • BCG tubercle bacteria
  • Subcellular, soluble tumor-associated antigens e.g. Proteins or peptides with corresponding immunodominant epitopes from melanoma cells (van der Bruggen et al., Science 254, 1643-1647 (1991), adenocarcinomas (Taylor-Papadimitriou et al., Ann NY Acad Sei 690, 69-79 (1993) ) or other tumors (Slingluff et al., Curr Opin Immunol 6, 733-740 (1994)) must be bound to an immunogenic carrier molecule in order to increase their weak immunogenicity or to make them immunogenic at all.
  • an immunogenic carrier molecule in order to increase their weak immunogenicity or to make them immunogenic at all.
  • Peptides without Carrier molecules generally only act as haptens, ie, although they react with a corresponding peptide-specific antibody, but cannot themselves elicit an immune response, certain serum proteins or bacterial toxoids are used as the carrier molecule.
  • the conjugate of peptide and carrier molecule is used Usually an adjuvant is added, which further strengthens the immune response.
  • the immune response is recognizable from the formation of antigen-specific antibodies and / or T lymphocytes.
  • T-lymphocyte-mediated immunity As results from animal experiments and in vitro tests with human tumor cells show, the generation of a therapeutic effective immune response against cancer cells primarily to T-lymphocyte-mediated immunity and less to the formation of antibodies (Hellström and Hellström, Ann NY Acad Sei 690, 24-33 (1993)).
  • the aim of the present invention was therefore to provide a tumor vaccine which makes it possible to use both tumor cells and tumor-associated antigens or antigenic structures for an effective defense reaction against native tumor cells.
  • the object of the invention was to effectively increase the immunogenicity of tumor cells, tumor-associated antigens or antigenic substructures used as vaccines by genetic modification of the tumor cells or by bio-chemical modification of tumor-associated antigens or antigenic substructures, and in particular by To stimulate T-lymphocyte mediated immunity.
  • tumor cells which, according to the invention, additionally contain the gene of an exogenous heat shock protein or by binding tumor-associated antigens or antigenic substructures to an exogenous heat shock protein.
  • the tumor vaccine according to the invention contains tumor cells which contain the gene of an exogenous heat shock protein or tumor-associated antigens or antigenic substructures which are bound to an exogenous heat shock protein.
  • a microbial heat shock protein or its gene is preferably used.
  • the gene of heat shock proteins or heat shock proteins from Mycobacteria, Escherichia coli and from Chlamydia trachomatis are particularly preferred, in particular it is the heat shock proteins HSP65 and HSP70 from Mycobacteria, HSP70 from Escherichia coli (DnaK) and HSP60 and HSP70 from Chlamydia tris.
  • Autologous tumor cells which are isolated from surgically removed tumor tissue using mechanical or enzymatic methods are suitable for producing the tumor vaccine.
  • Tumor cell lines derived from allogeneic tumors of the same histology can also be used, an example of which are cells from a colon carcinoma line, such as e.g. the lines LS174T or LOVO.
  • the vaccine is administered postoperatively, before application the tumor cells are devitalized by radioactive radiation.
  • the gene of an exogenous heat shock protein and its expression the tumor cells are permanently alienated and thus more immunogenic.
  • the gene of the heat shock protein is e.g. inserted into the vector pcDNA3 (Invitrogen Corp.).
  • tumor vaccines can be produced for the treatment of patients with carcinoma, sarcoma, malignant melanoma, leukemia or malignant lymphoma.
  • biochemically isolated tumor-associated antigens and synthetically produced antigens are also b
  • a tumor-associated antigen is, for example, the carcinoembryonic antigen.
  • Synthetically produced mucin peptides, in particular monomers and oligomers of the mucin peptides MUC1 and MUC2, are used as synthetically produced antigenic partial structures.
  • the tumor vaccine is produced by conventional methods under sterile cauldrons, in which the heat shock protein is chemically bound to the tumor-associated antigens or antigenic substructures.
  • a novel strategy is being pursued with the tumor vaccine according to the invention.
  • the genetic engineering modification of tumor cells with the gene of a heat shock protein or by binding to an exogenous heat shock protein surprisingly effectively increases the immunogenicity of tumor cells and of tumor-associated antigens or antigenic substructures, i.e. This makes it possible for the first time to use tumor-associated antigens or antigenic substructures in a targeted manner and thereby stimulate the immunity mediated by T lymphocytes.
  • the tumor vaccines according to the invention are used for the treatment of patients with carcinoma, sarcoma or malignant melanoma and are preferably administered postoperatively.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention concerne un vaccin antitumoral dans lequel l'immunogénicité des cellules tumorales, des antigènes associés aux cellules ou des structures antigéniques partielles est renforcée par modification génétique ou par liaison chimique à une protéine de choc thermique exogène. On utilise de préférence des protéines de choc d'origine microbienne ou leurs gènes, qui sont obtenus à partir de mycobactéries, Escherichia coli ou Chlamydia trachomatis.
PCT/DE1997/000172 1996-01-27 1997-01-27 Vaccin antitumoral pour le traitement immunitaire des tumeurs malignes WO1997026910A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE19602985A DE19602985A1 (de) 1996-01-27 1996-01-27 Tumorzellimpfstoff für die Immuntheraphie von malignen Tumoren
DE19602985.6 1996-01-27
DE19604380A DE19604380A1 (de) 1996-02-07 1996-02-07 Tumorimpfstoff für die Immuntherapie von malignen Tumoren
DE19604380.8 1996-02-07

Publications (2)

Publication Number Publication Date
WO1997026910A2 true WO1997026910A2 (fr) 1997-07-31
WO1997026910A3 WO1997026910A3 (fr) 1997-10-02

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Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998023735A1 (fr) * 1996-11-26 1998-06-04 Stressgen Biotechnologies Corp. Reponses immunes mettant en oeuvre des compositions contenant des proteines de stress
US5830464A (en) * 1997-02-07 1998-11-03 Fordham University Compositions and methods for the treatment and growth inhibition of cancer using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy
US5837251A (en) * 1995-09-13 1998-11-17 Fordham University Compositions and methods using complexes of heat shock proteins and antigenic molecules for the treatment and prevention of neoplastic diseases
US5935576A (en) * 1995-09-13 1999-08-10 Fordham University Compositions and methods for the treatment and prevention of neoplastic diseases using heat shock proteins complexed with exogenous antigens
US5948646A (en) * 1997-12-11 1999-09-07 Fordham University Methods for preparation of vaccines against cancer comprising heat shock protein-peptide complexes
US5961979A (en) * 1994-03-16 1999-10-05 Mount Sinai School Of Medicine Of The City University Of New York Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens
US5985270A (en) * 1995-09-13 1999-11-16 Fordham University Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes
US5997873A (en) * 1994-01-13 1999-12-07 Mount Sinai School Of Medicine Of The City University Of New York Method of preparation of heat shock protein 70-peptide complexes
US6017540A (en) * 1997-02-07 2000-01-25 Fordham University Prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases with heat shock/stress protein-peptide complexes
US6130087A (en) * 1996-10-07 2000-10-10 Fordham University Methods for generating cytotoxic T cells in vitro
WO2001051081A1 (fr) * 2000-01-14 2001-07-19 Whitehead Institute For Biomedical Research L'elicitation in vivo des ctl par des proteines de fusion de la proteine de choc thermique correspond a un domaine discret de liaison de l'atp et est independante des cellules cd4?+¿
US6331299B1 (en) 1995-08-18 2001-12-18 Sloan-Kettering Institute For Cancer Research Method for treatment of cancer and infectious disease and compositions useful in same
US6451316B1 (en) 1998-10-05 2002-09-17 University Of Conneticut Health Center Methods for generating antigen-reactive T cells in vitro
US6495347B1 (en) 1999-07-08 2002-12-17 Stressgen Biotechnologies Corporation Induction of a Th1-like response in vitro
US6497880B1 (en) 1998-12-08 2002-12-24 Stressgen Biotechnologies Corporation Heat shock genes and proteins from Neisseria meningitidis, Candida glabrata and Aspergillus fumigatus
US6524825B1 (en) 1997-08-05 2003-02-25 Stressgen Biotechnologies, Inc. Immune responses against HPV antigens elicited by compositions comprising an HPV antigen and a stress protein or an expression vector capable of expression of these proteins
US6605464B1 (en) 1995-08-18 2003-08-12 Sloan-Kettering Institute For Cancer Research Method of treatment of cancer and infectious disease and compositions useful in same
US6719974B1 (en) 1995-08-18 2004-04-13 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6761892B1 (en) 1995-08-18 2004-07-13 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6773707B1 (en) 1995-08-18 2004-08-10 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6797491B2 (en) 2000-06-26 2004-09-28 Stressgen Biotechnologies Corporation Human papilloma virus treatment
US6921534B2 (en) 2001-02-05 2005-07-26 Stressgen Biotechnologies Corporation Hepatitis B virus treatment
US6984384B1 (en) 1999-09-30 2006-01-10 Health Research, Inc. Stress protein compositions and methods for prevention and treatment of cancer and infectious disease
US7157089B1 (en) 1996-11-26 2007-01-02 Stressgen Biotechnologies Corporation Immune responses using compositions containing stress proteins
US7309491B2 (en) 2003-04-11 2007-12-18 Antigenics Inc. Heat shock protein-based vaccines and immunotherapies
US7378096B2 (en) 1999-09-30 2008-05-27 Health Research, Inc. Stress protein compositions and methods for prevention and treatment of cancer and infectious disease
US7420037B2 (en) 2003-02-13 2008-09-02 Antigenics Inc. Heat shock protein-based vaccines and immunotherapies
US7449557B2 (en) 2000-06-02 2008-11-11 University Of Connecticut Health Center Complexes of alpha (2) macroglobulin and antigenic molecules for immunotherapy
US7501234B2 (en) 1989-06-15 2009-03-10 Whitehead Institute For Biomedical Research Stress proteins and uses therefor
US7666581B2 (en) 2001-08-20 2010-02-23 University Of Connecticut Health Center Methods for preparing compositions comprising heat shock proteins useful for the treatment of cancer and infectious disease
US8475785B2 (en) 2008-03-03 2013-07-02 The University Of Miami Allogeneic cancer cell-based immunotherapy
US8685384B2 (en) 1998-02-20 2014-04-01 University Of Miami Recombinant cancer cell secreting modified heat shock protein-antigenic peptide complex
US10046047B2 (en) 2015-02-06 2018-08-14 Heat Biologics, Inc. Vector co-expressing vaccine and costimulatory molecules
EP3373961A4 (fr) * 2015-11-10 2019-07-31 Ohio State Innovation Foundation Méthodes et compositions associées à une affinité humorale accélérée
US11548930B2 (en) 2017-04-04 2023-01-10 Heat Biologics, Inc. Intratumoral vaccination
US11666649B2 (en) 2016-10-11 2023-06-06 University Of Miami Vectors and vaccine cells for immunity against Zika virus

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AU2009226077B2 (en) 2008-03-20 2012-04-19 University Of Miami Heat shock protein gp96 vaccination and methods of using same

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US7501234B2 (en) 1989-06-15 2009-03-10 Whitehead Institute For Biomedical Research Stress proteins and uses therefor
US5997873A (en) * 1994-01-13 1999-12-07 Mount Sinai School Of Medicine Of The City University Of New York Method of preparation of heat shock protein 70-peptide complexes
US6168793B1 (en) 1994-01-13 2001-01-02 Mount Sinai School Of Medicine Of New York University Heat shock protein 70 preparations in vaccination against cancer and infectious disease
US6455503B1 (en) 1994-03-16 2002-09-24 Mount Sinai School Of Medicine Of New York University Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens
US6048530A (en) * 1994-03-16 2000-04-11 Mount Sinai School Of Medicine Of New York University Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens
US5961979A (en) * 1994-03-16 1999-10-05 Mount Sinai School Of Medicine Of The City University Of New York Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens
US6331299B1 (en) 1995-08-18 2001-12-18 Sloan-Kettering Institute For Cancer Research Method for treatment of cancer and infectious disease and compositions useful in same
US6605464B1 (en) 1995-08-18 2003-08-12 Sloan-Kettering Institute For Cancer Research Method of treatment of cancer and infectious disease and compositions useful in same
US6719974B1 (en) 1995-08-18 2004-04-13 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6773707B1 (en) 1995-08-18 2004-08-10 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6761892B1 (en) 1995-08-18 2004-07-13 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US7618637B2 (en) 1995-08-18 2009-11-17 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6641812B2 (en) 1995-08-18 2003-11-04 Sloan Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6656679B2 (en) 1995-08-18 2003-12-02 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6663868B1 (en) 1995-08-18 2003-12-16 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6673348B2 (en) 1995-08-18 2004-01-06 Sloan-Kettering Institute For Cancer Research Heat shock protein-based vaccines and immunotherapies
US6139841A (en) * 1995-09-13 2000-10-31 Fordham University Compositions and methods using complexes of heat shock protein 70 and antigenic molecules for the treatment and prevention of infectious diseases
US6136315A (en) * 1995-09-13 2000-10-24 Fordham University Compositions and methods using complexes of heat shock protein 70 and antigenic molecules for the treatment and prevention of neoplastic diseases
US6187312B1 (en) 1995-09-13 2001-02-13 Fordham University Compositions and methods using complexes of heat shock protein 90 and antigenic molecules for the treatment and prevention of infectious diseases
US6156302A (en) * 1995-09-13 2000-12-05 Fordham University Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes
US6143299A (en) * 1995-09-13 2000-11-07 Fordham University Compositions and methods using complexes of heat shock protein gp96 and antigenic molecules for the treatment and prevention of infectious diseases
US6447781B1 (en) 1995-09-13 2002-09-10 Fordham University Therapeutic and prophylactic methods using heat shock proteins
US5935576A (en) * 1995-09-13 1999-08-10 Fordham University Compositions and methods for the treatment and prevention of neoplastic diseases using heat shock proteins complexed with exogenous antigens
US5837251A (en) * 1995-09-13 1998-11-17 Fordham University Compositions and methods using complexes of heat shock proteins and antigenic molecules for the treatment and prevention of neoplastic diseases
US6162436A (en) * 1995-09-13 2000-12-19 Fordham University Compositions and methods using complexes of heat shock protein 90 and antigenic molecules for the treatment and prevention of neoplastic diseases
US5985270A (en) * 1995-09-13 1999-11-16 Fordham University Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes
US7601359B1 (en) 1995-09-13 2009-10-13 Fordham University Compositions and methods for the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases with heat shock/stress proteins
US6410028B1 (en) 1995-09-13 2002-06-25 Fordham University Therapeutic and prophylactic methods using heat shock proteins
US6461615B1 (en) 1995-09-13 2002-10-08 Fordham University Therapeutic and prophylactic methods using heat shock proteins
US6030618A (en) * 1995-09-13 2000-02-29 Fordham University Therapeutic and prophylactic methods using heat shock proteins
US6130087A (en) * 1996-10-07 2000-10-10 Fordham University Methods for generating cytotoxic T cells in vitro
WO1998023735A1 (fr) * 1996-11-26 1998-06-04 Stressgen Biotechnologies Corp. Reponses immunes mettant en oeuvre des compositions contenant des proteines de stress
US7157089B1 (en) 1996-11-26 2007-01-02 Stressgen Biotechnologies Corporation Immune responses using compositions containing stress proteins
US6403095B1 (en) 1997-02-07 2002-06-11 Fordham University Treatment of primary and metastatic neoplastic diseases with HSP70-peptide complexes
US6387374B1 (en) 1997-02-07 2002-05-14 Fordham University Treatment of primary and metastatic neoplastic diseases with hsp90-peptide complexes
US6322790B1 (en) 1997-02-07 2001-11-27 Fordham University Compositions and methods for eliciting an immune response using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy
US6455048B1 (en) 1997-02-07 2002-09-24 Fordham University Prevention of primary and metastatic neoplastic diseases with hsp70-peptide complexes
US6447780B1 (en) 1997-02-07 2002-09-10 Fordham University Prevention of primary and metastatic neoplastic diseases with hsp90-peptide complexes
US5830464A (en) * 1997-02-07 1998-11-03 Fordham University Compositions and methods for the treatment and growth inhibition of cancer using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy
US6383493B1 (en) 1997-02-07 2002-05-07 Fordham University Methods and compositions for eliciting an immune response with hsp70-peptide complexes
US6383494B1 (en) 1997-02-07 2002-05-07 Fordham University Methods and composition for eliciting an immune response with gp96-peptide complexes
US6017540A (en) * 1997-02-07 2000-01-25 Fordham University Prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases with heat shock/stress protein-peptide complexes
US6399070B1 (en) 1997-02-07 2002-06-04 Fordham University Methods and compositions for eliciting an immune response with hsp90-peptide complexes
US6436404B1 (en) 1997-02-07 2002-08-20 Fordham University Prevention of primary and metastatic neoplastic diseases with GP96-peptide complexes
US6524825B1 (en) 1997-08-05 2003-02-25 Stressgen Biotechnologies, Inc. Immune responses against HPV antigens elicited by compositions comprising an HPV antigen and a stress protein or an expression vector capable of expression of these proteins
US6900035B2 (en) 1997-08-05 2005-05-31 Stressgen Biotechnologies, Inc. Immune responses against HPV antigens elicited by compositions comprising an HPV antigen and a stress protein or an expression vector capable of expression of these proteins
US7262014B2 (en) 1997-08-05 2007-08-28 Stressgen Biotechnologies Corporation Immune responses against HPV antigens elicited by compositions comprising an HPV antigen and a stress protein or an expression vector capable of expression of these proteins
US6410027B1 (en) 1997-12-11 2002-06-25 Fordham University Methods for preparation of vaccines against cancer
US5948646A (en) * 1997-12-11 1999-09-07 Fordham University Methods for preparation of vaccines against cancer comprising heat shock protein-peptide complexes
US6406700B1 (en) 1997-12-11 2002-06-18 Fordham University Methods for preparation of vaccines against cancer
US6410026B1 (en) 1997-12-11 2002-06-25 Fordham University Methods for preparation of vaccines against cancer
US8685384B2 (en) 1998-02-20 2014-04-01 University Of Miami Recombinant cancer cell secreting modified heat shock protein-antigenic peptide complex
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