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Showing papers by "Pramod K. Srivastava published in 1998"


Journal ArticleDOI
01 Jun 1998-Immunity
TL;DR: It is conceivable that in a less polymorphic era, when adaptive immune response was but a distant gleam in the evolutionary eye, the interaction of HSPs with macrophage-like cells, leading to stimulation of the macrophages to secrete IL-1 and other messengers, was the primary “innate” defense mechanism.

583 citations


Patent
09 Sep 1998
TL;DR: In this paper, the authors present methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases, which include administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule.
Abstract: The invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. “Antigenic molecule” as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp70, 50-1000 micrograms for hsp90, and 10-600 micrograms for gp96. The invention also provides a method for measuring tumor rejection in vivo in an individual, preferably a human, comprising measuring the generation by the individual of MHC Class I-restricted CD8+cytotoxic T lymphocytes specific to the tumor. Methods of purifying hsp70-peptide complexes are also provided.

90 citations


Journal ArticleDOI
TL;DR: Potent and specific tumor antigens have long been the holy grail in cancer immunotherapy; HSPPCs from tumor cells could become a safe and reliable source of tumor-specific antIGens for clinical application.

85 citations


Patent
14 Oct 1998
TL;DR: In this paper, heat shock proteins, including gp96, hsp90, and hsp70, are disclosed for treating a variety of autoimmune diseases, including insulin dependent diabetes mellitus.
Abstract: The invention relates to methods and compositions for the treatment of autoimmune disease. Specifically, compositions comprising heat shock proteins, including gp96, hsp90, and hsp70, are disclosed. Immunotherapeutic methods for administering the hsp-containing compositions are disclosed. Furthermore, methods for preventing rejection of organs transplanted to treat autoimmune disease are disclosed. The disclosed methods are useful for treating a variety of autoimmune diseases, including insulin dependent diabetes mellitus.

74 citations


Journal ArticleDOI
TL;DR: It is established that administration of gp96 results in generation of tumor-specific cytotoxic T lymphocyte response in addition to protective immunity, and results indicate that gp96 preparations elicit a memory T cell response that is capable of being recalled.
Abstract: Tumor-derived heat shock proteins have been shown previously to elicit specific prophylactic immunity to cognate tumors Here we establish that administration of gp96 results in generation of tumor-specific cytotoxic T lymphocyte response in addition to protective immunity In one instance, gp96 preparations are shown to elicit an immune response against a tumor, where intact tumor cells are unable to do so Finally, our results indicate that gp96 preparations elicit a memory T cell response that is capable of being recalled

73 citations


Patent
03 Feb 1998
TL;DR: In this paper, the authors present methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases, which include administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule.
Abstract: not available for EP0973548Abstract of corresponding document: US6017540The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. Optionally, the methods further comprise administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex are in the range of 0.1 to 9.0 micrograms for complexes comprising hsp70, 5 to 49 micrograms for hsp90, and 0.1 to 9.0 micrograms for gp96.

57 citations


Patent
11 Dec 1998
TL;DR: In this paper, the authors proposed methods for preparing immunogenic, prophylactically and therapeutically effective complexes of heat shock proteins noncovalently associated with antigenic peptides of cancer cells.
Abstract: The present invention relates to methods for preparing immunogenic, prophylactically and therapeutically effective complexes of heat shock proteins noncovalently associated with antigenic peptides of cancer cells. The claimed methods comprise the constructing of a cDNA library from cancer or preneoplastic cell RNA, expressing the cDNA library in an appropriate host cell, and recovering the immunogenic complexes from the cells. Large amounts of such immunogenic complexes can be obtained by large-scale culturing of host cells containing the cDNA library. The complexes can be used as a vaccine to elicit specific immune responses against cancer or preneoplastic cells, and to treat or prevent cancer.

45 citations


Journal ArticleDOI
TL;DR: This paper deals with an adaptive technique for choosing local threshold values for faithful image segmentation using a modified Hopfield neural network and the results are compared with that of a potential surface interpolation method.

19 citations



Patent
16 Apr 1998
TL;DR: In this article, a method for inhibiting the proliferation of a tumor in a mammal is described. But the method involves the steps of (a) isolating a stress protein-peptide complex from tumor cells previously removed from the mammal and (b) administering the isolated PSP-complex along with a cytokine to the mammal in order to stimulate in the mammal an immune response against the tumor from which the complex was isolated.
Abstract: Disclosed is a method for inhibiting the proliferation of a tumor in a mammal. The method involves the steps of (a) isolating a stress protein-peptide complex from tumor cells previously removed from the mammal and (b) administering the isolated stress protein-peptide complex along with a cytokine to the mammal in order to stimulate in the mammal an immune response against the tumor from which the complex was isolated. Stress protein-peptide complexes having particular utility in the practice of the instant invention include the Hsp70-peptide, Hsp90-peptide and gp96-peptide complexes.

9 citations


Patent
03 Feb 1998
TL;DR: In this paper, the authors present methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases, which include administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule.
Abstract: not available for EP1001807Abstract of corresponding document: US5830464The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule in combination with administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex when administered intradermally are in the range of 0.1 to 9.0 micrograms for complexes comprising hsp70, 5 to 49 micrograms for hsp90, and 0.1 to 9.0 micrograms for gp96. In another embodiment, the effective amounts of the complex when administered subcutaneously are in the range of 10 to 600 micrograms for complexes comprising hsp70, 50 to 5000 micrograms for hsp90, and 10 to 600 micrograms for gp96.

Journal ArticleDOI
TL;DR: This broad and general principle is the basis for a new generation of vaccines against cancers and infectious diseases and circumvents the need for identification of the T cell epitopes for any given cancer or infectious agent.
Abstract: Heat shock proteins (HSPs) are associatedin vivo with the entire repertoire of peptides (antigenic and otherwise) generated within that cell. Immunization with such HSP-peptide complexes is unusually efficient in eliciting cellular immune responses against the antigenic peptides associated with the HSPs. This broad and general principle is the basis for a new generation of vaccines against cancers and infectious diseases and circumvents the need for identification of the T cell epitopes for any given cancer or infectious agent.