DE19602985A1 - Tumorzellimpfstoff für die Immuntheraphie von malignen Tumoren - Google Patents
Tumorzellimpfstoff für die Immuntheraphie von malignen TumorenInfo
- Publication number
- DE19602985A1 DE19602985A1 DE19602985A DE19602985A DE19602985A1 DE 19602985 A1 DE19602985 A1 DE 19602985A1 DE 19602985 A DE19602985 A DE 19602985A DE 19602985 A DE19602985 A DE 19602985A DE 19602985 A1 DE19602985 A1 DE 19602985A1
- Authority
- DE
- Germany
- Prior art keywords
- tumor cells
- tumor
- cell vaccine
- gene
- tumor cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 14
- 238000011282 treatment Methods 0.000 title claims description 6
- 208000032839 leukemia Diseases 0.000 title claims description 4
- 201000009030 Carcinoma Diseases 0.000 title claims description 3
- 201000001441 melanoma Diseases 0.000 title claims description 3
- 229960005486 vaccine Drugs 0.000 title abstract description 5
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 25
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 13
- 102000002812 Heat-Shock Proteins Human genes 0.000 claims abstract description 12
- 108010004889 Heat-Shock Proteins Proteins 0.000 claims abstract description 12
- 238000009169 immunotherapy Methods 0.000 claims abstract description 3
- 229940030325 tumor cell vaccine Drugs 0.000 claims description 17
- 241000606153 Chlamydia trachomatis Species 0.000 claims description 4
- 229940038705 chlamydia trachomatis Drugs 0.000 claims description 4
- 241000588724 Escherichia coli Species 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 230000000735 allogeneic effect Effects 0.000 claims description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 2
- 230000000813 microbial effect Effects 0.000 claims description 2
- 101710163595 Chaperone protein DnaK Proteins 0.000 claims 3
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 claims 3
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 claims 3
- 102100021410 Heat shock 70 kDa protein 14 Human genes 0.000 claims 1
- 101001041756 Homo sapiens Heat shock 70 kDa protein 14 Proteins 0.000 claims 1
- 101000944608 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Chaperonin GroEL 2 Proteins 0.000 claims 1
- 201000011510 cancer Diseases 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 101000839464 Leishmania braziliensis Heat shock 70 kDa protein Proteins 0.000 description 3
- 230000007123 defense Effects 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 2
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101000738180 Euglena gracilis Chaperonin CPN60, mitochondrial Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
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
- A61K39/001176—Heat shock 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
- A61K2039/51—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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
Die Erfindung betrifft die Herstellung eines gentechnisch
modifizierten Tumorzellimpfstoffes für die Immuntherapie von
malignen Tumoren. Anwendungsgebiete der Erfindung sind die
Medizin und die pharmazeutische Industrie.
Die grundlegende Behandlung von Patienten mit einem soliden
malignen Tumor ist die chirurgische oder strahlen
therapeutische Entfernung des Primärtumors. Allerdings
besteht auch nach kompletter Entfernung des Primärtumors das
Risiko, daß Mikrometastasen, die bereits zum Zeitpunkt der
Operation existierten, in der postoperativen Phase zu
lebensbedrohlichen Metastasen auswachsen. Um die Metastasen
zu bekämpfen, wird neben einer chemotherapeutischen
Behandlung der Patienten auch versucht, die immunologische
Abwehrbereitschaft des Patienten gegen die Tumorzellen
wirksam zu stärken. Dies kann durch eine aktive spezifische
oder passive Immunisierung geschehen. Die aktive spezifische
Immunisierung verfolgt das Ziel, das Immunsystem des
Patienten durch Impfung mit devitalisierten Tumorzellen oder
definierten tumorassoziierten Antigenen derart zu aktivieren,
daß tumorspezifische Abwehrzellen oder Antikörper gebildet
werden, die die Mikrometastasen eliminieren oder zumindest
deren Wachstum merklich hemmen. Diese Therapieform kann auch
zur Behandlung von Patienten mit Leukämie in der
Remissionsphase eingesetzt werden. Eine Variante der aktiven
spezifischen Immunisierung besteht darin, daß man Immunzellen
des Patienten extrakorporal, in der Zellkultur mit Hilfe
devitalisierter Tumorzellen oder definierter löslicher
tumorassoziierter Antigene tumorspezifisch aktiviert und
vermehrt und die derart aktivierten Immunzellen in den
Patienten retransfundiert.
Nachteilig für die aktive spezifische Immunisierung ist, daß
die Tumorzellen des Menschen in den meisten Fällen eine zu
geringe Immunogenität besitzen, um per se eine wirksame
immunologische Abwehrreaktion auslösen zu können. Daher ist
man darauf angewiesen, die Immunogenität der als Impfstoff
vorgesehenen Tumorzellen künstlich zu erhöhen. Dieses kann
dadurch geschehen, daß man die Tumorzellen chemisch oder
enzymatisch verändert (Prager et. al., Ann NY Acad Sci 276,
61-64 (1976)). Auch ein Hinzufügen apathogener Viren
(Cassel et. al, Cancer 52, 856-860 (1983)) oder
abgeschwächter Tuberkelbakterien/BCG/(Hanna et. al.,
Cancer Immunol Immunother 7, 165-173 (1979)) kann die
Immunogenität eines Tumorzellimpfstoffes steigern. Mit Hilfe
der Gentechnik hat man Gene unterschiedlicher Wirkstoffe in
Tumorzellen übertragen, ebenfalls mit der Zielstellung, die
von dem Tumorzellimpfstoff ausgelöste Immunantwort zu
verstärken (Pardoll, Curr Opin Immunol 4, 619-623 (1992)).
Der Gentransfer in Tumorzellen betrifft u. a. Zytokine,
Interferone, Kolonie-stimulierende Faktoren, Histokompati
bilitätsantigene oder costimulatorisch wirkende Faktoren der
Immunantwort, sämtlich Wirkstoffe humaner Herkunft. Trotz
mancher Erfolge ist es aber bisher nicht gelungen, einen
klinisch überzeugenden Tumorzellimpfstoff zu entwickeln.
Das Ziel der vorliegenden Erfindung ist es, die Immunogenität
der als Impfstoff verwendeten Tumorzellen durch gentechnische
Modifizierung der Tumorzellen wirksam zu verstärken.
Dieses Ziel wird erfindungsgemäß durch einen
Tumorzellimpfstoff erreicht, der aus Tumorzellen besteht, die
zusätzlich das Gen eines exogenen Hitzeschockproteins
enthalten. Die wichtigste Ausführungsform der Erfindung
besteht darin, das Gen eines mikrobiellen Hitzeschockproteins
zu verwenden. Bevorzugt ist der Einsatz von
Hitzeschockproteinen aus Mycobakterien, Escherichia coli und
aus Chlamydia trachomatis. Besonders bevorzugt sind die
Hitzeschockproteine HSP 65 und HSP 70 aus Mycobakterien, HSP
70 aus Escherichia coli (DnaK) sowie HSP 60 und HSP 70 aus
Chlamydia trachomatis.
Zur Herstellung des Tumorzellimpfstoffes eignen sich autologe
Tumorzellen, die mit Hilfe mechanischer oder enzymatischer
Methoden aus chirurgisch entferntem Tumorgewebe isoliert
werden. Tumorzellinien, die von allogenen Tumoren gleicher
Histologie stammen, können ebenfalls verwendet werden, ein
Beispiel dafür sind Zellen einer Colonkarzinomlinie. Der
Tumorzellimpfstoff wird postoperativ verabfolgt, vor der
Applikation werden die Tumorzellen durch radioaktive
Bestrahlung devitalisiert.
Mit der Herstellung des erfindungsgemäßen Tumorzell
impfstoffes wird eine neuartige Strategie verfolgt. Durch
Einschleusen des Gens eines exogenen Hitzeschockproteins und
dessen Expression werden die Tumorzellen nachhaltig
verfremdet und damit stärker immunogen. Nach dieser Strategie
können Tumorzellimpfstoffe für die Behandlung von Patienten
mit Karzinom, Sarkom, malignem Melanom, Leukämie oder
malignem Lymphom hergestellt werden.
Claims (9)
1. Tumorzellimpfstoff für die Immuntherapie von Tumoren
bestehend aus Tumorzellen, die zusätzlich das Gen eines
exogenen Hitzeschockproteins enthalten.
2. Tumorzellimpfstoff nach Anspruch 1, dadurch
gekennzeichnet, daß die Tumorzellen das Gen eines
mikrobiellen Hitzeschockproteins enthalten.
3. Tumorzellimpfstoff nach Anspruch 1 und 2, dadurch
gekennzeichnet, daß die Tumorzellen das Gen des
Hitzeschockproteins HSP65 aus Mycobakterien enthalten.
4. Tumorzellimpfstoff nach Anspruch 1 und 2, dadurch
gekennzeichnet, daß die Tumorzellen das Gen des
Hitzeschockproteins HSP70 aus Mycobakterien enthalten.
5. Tumorzellimpfstoff nach Anspruch 1 und 2, dadurch
gekennzeichnet, daß die Tumorzellen das Gen des
Hitzeschockproteins HSP70 aus Escherichia coli (DnaK)
enthalten.
6. Tumorzellimpfstoff nach Anspruch 1 und 2, dadurch
gekennzeichnet, daß die Tumorzellen das Gen des
Hitzeschockproteins HSP60 aus Chlamydia trachomatis enthalten.
7. Tumorzellimpfstoff nach Anspruch 1 und 2, dadurch
gekennzeichnet, daß die Tumorzellen das Gen des
Hitzeschockproteins HSP70 aus Chlamydia trachomatis enthalten.
8. Tumorzellimpfstoff nach Anspruch 1-7, dadurch
gekennzeichnet, daß als Tumorzellen devitalisierte autologe
oder allogene Tumorzellen eingesetzt werden.
9. Verwendung des Tumorzellimpfstoffes nach Anspruch 1-8 zur
Behandlung von Patienten mit Karzinom, Sarkom, malignem
Melanom, Leukämie oder malignem Lymphom.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19602985A DE19602985A1 (de) | 1996-01-27 | 1996-01-27 | Tumorzellimpfstoff für die Immuntheraphie von malignen Tumoren |
| PCT/DE1997/000172 WO1997026910A2 (de) | 1996-01-27 | 1997-01-27 | Tumorimpfstoff für die immuntherapie von malignen tumoren |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19602985A DE19602985A1 (de) | 1996-01-27 | 1996-01-27 | Tumorzellimpfstoff für die Immuntheraphie von malignen Tumoren |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19602985A1 true DE19602985A1 (de) | 1997-07-31 |
Family
ID=7783887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19602985A Withdrawn DE19602985A1 (de) | 1996-01-27 | 1996-01-27 | Tumorzellimpfstoff für die Immuntheraphie von malignen Tumoren |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE19602985A1 (de) |
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| US6156302A (en) * | 1995-09-13 | 2000-12-05 | Fordham University | Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes |
| US6451316B1 (en) | 1998-10-05 | 2002-09-17 | University Of Conneticut Health Center | Methods for generating antigen-reactive T cells in vitro |
| US7449557B2 (en) | 2000-06-02 | 2008-11-11 | University Of Connecticut Health Center | Complexes of alpha (2) macroglobulin and antigenic molecules for immunotherapy |
| 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 |
| US8541002B2 (en) | 2003-09-12 | 2013-09-24 | Agenus Inc. | Vaccine for treatment and prevention of herpes simplex virus infection |
| 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 |
| US10568948B2 (en) | 2015-05-13 | 2020-02-25 | Agenus Inc. | Vaccines for treatment and prevention of cancer |
| US11065317B2 (en) | 2018-04-26 | 2021-07-20 | Agenus Inc. | Heat shock protein-binding peptide compositions and methods of use thereof |
| 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 |
-
1996
- 1996-01-27 DE DE19602985A patent/DE19602985A1/de not_active Withdrawn
Cited By (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US6410028B1 (en) | 1995-09-13 | 2002-06-25 | 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 |
| US6030618A (en) * | 1995-09-13 | 2000-02-29 | Fordham University | Therapeutic and prophylactic methods using heat shock proteins |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| US6156302A (en) * | 1995-09-13 | 2000-12-05 | Fordham University | Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes |
| 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 |
| US6447781B1 (en) | 1995-09-13 | 2002-09-10 | Fordham University | Therapeutic and prophylactic methods using heat shock proteins |
| 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 |
| US6461615B1 (en) | 1995-09-13 | 2002-10-08 | 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 |
| US6436404B1 (en) | 1997-02-07 | 2002-08-20 | Fordham University | Prevention of primary and metastatic neoplastic diseases with GP96-peptide complexes |
| US6447780B1 (en) | 1997-02-07 | 2002-09-10 | Fordham University | Prevention of primary and metastatic neoplastic diseases with hsp90-peptide complexes |
| US6399070B1 (en) | 1997-02-07 | 2002-06-04 | Fordham University | Methods and compositions for eliciting an immune response with hsp90-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 |
| 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 |
| 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 |
| US6383493B1 (en) | 1997-02-07 | 2002-05-07 | Fordham University | Methods and compositions for eliciting an immune response with hsp70-peptide complexes |
| US6403095B1 (en) | 1997-02-07 | 2002-06-11 | Fordham University | Treatment of primary and metastatic neoplastic diseases with HSP70-peptide complexes |
| US6455048B1 (en) | 1997-02-07 | 2002-09-24 | Fordham University | Prevention of primary and metastatic neoplastic diseases 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 |
| US6410027B1 (en) | 1997-12-11 | 2002-06-25 | Fordham University | Methods for preparation of vaccines against cancer |
| 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 |
| US5948646A (en) * | 1997-12-11 | 1999-09-07 | Fordham University | Methods for preparation of vaccines against cancer comprising heat shock protein-peptide complexes |
| US8685384B2 (en) | 1998-02-20 | 2014-04-01 | University Of Miami | Recombinant cancer cell secreting modified heat shock protein-antigenic peptide complex |
| US6451316B1 (en) | 1998-10-05 | 2002-09-17 | University Of Conneticut Health Center | Methods for generating antigen-reactive T cells in vitro |
| US7449557B2 (en) | 2000-06-02 | 2008-11-11 | University Of Connecticut Health Center | Complexes of alpha (2) macroglobulin and antigenic molecules for immunotherapy |
| 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 |
| US8541002B2 (en) | 2003-09-12 | 2013-09-24 | Agenus Inc. | Vaccine for treatment and prevention of herpes simplex virus infection |
| US8475785B2 (en) | 2008-03-03 | 2013-07-02 | The University Of Miami | Allogeneic cancer cell-based immunotherapy |
| US9238064B2 (en) | 2008-03-03 | 2016-01-19 | University Of Miami | Allogeneic cancer cell-based immunotherapy |
| US10046047B2 (en) | 2015-02-06 | 2018-08-14 | Heat Biologics, Inc. | Vector co-expressing vaccine and costimulatory molecules |
| US10758611B2 (en) | 2015-02-06 | 2020-09-01 | Heat Biologics, Inc. | Vector co-expressing vaccine and costimulatory molecules |
| US10780161B2 (en) | 2015-02-06 | 2020-09-22 | Heat Biologics, Inc. | Vector co-expressing vaccine and costimulatory molecules |
| US10568948B2 (en) | 2015-05-13 | 2020-02-25 | Agenus Inc. | Vaccines for treatment and prevention of cancer |
| US11666649B2 (en) | 2016-10-11 | 2023-06-06 | University Of Miami | Vectors and vaccine cells for immunity against Zika virus |
| US11548930B2 (en) | 2017-04-04 | 2023-01-10 | Heat Biologics, Inc. | Intratumoral vaccination |
| US11065317B2 (en) | 2018-04-26 | 2021-07-20 | Agenus Inc. | Heat shock protein-binding peptide compositions and methods of use thereof |
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