Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Conjugate or complex
Reexamination Certificate
1998-09-09
2001-02-13
Bansal, Geetha P. (Department: 1642)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Conjugate or complex
C424S184100, C424S194100, C424S196110, C424S197110, C424S265100, C424S274100, C424S277100
Reexamination Certificate
active
06187312
ABSTRACT:
TABLE OF CONTENTS
1. INTRODUCTION
2. BACKGROUND OF THE INVENTION
2.1. Tumor-Specific Immunogenicities of Heat Shock/Stress Proteins hsp70. hsp90 and gp96
2.2. Pathobiology of Cancer
2.3. Immunotherapy
2.3.1. Interleukins (IL-2, IL-4 and IL-6)
2.3.2. Tumor Necrosis Factor
2.3.3. Interferons
2.4. Pharmacokinetic Models for Anticancer Chemotherapeutic and Immunotherapeutic Drugs: Extrapolation and Scaling of Animal Data to Humans
3. SUMMARY OF THE INVENTION
4. BRIEF DESCRIPTION OF FIGURES
5. DETAILED DESCRIPTION OF THE INVENTION
5.1. Dosage Regimens
5.2. Therapeutic Compositions for Immune Responses to Cancer
5.2.1. Preparation and Purification of Hsp 70-Peptide Complexes
5.2.2. Preparation and Purification of Hsp 90-peptide complexes
5.2.3. Preparation and Purification of gp96-Peptide Complexes
5.2.4. Isolation of Antigenic/Immunogenic Components
5.2.4.1 Peptides From Stress Protein-Peptide Complexes
5.2.4.2 Peptides from MHC-Peptide Complexes
5.2.5 Exogenous Antigenic Molecules
5.2.6 In Vitro Production of Stress Protein-Antigenic Molecule Complexes
5.2.7 Determination of Immunogenicity of Stress Protein-Peptide Complexes
5.3. Formulation
5.4 Target Infectious Diseases
5.5. Target Cancers
5.5.1. Colorectal Cancer Metastatic to the Liver
5.5.2. Hepatocellular Carcinoma
5.5.3. Breast Cancer
5.6. Autologous Embodiment
5.7. Prevention and Treatment of Primary and Metastatic Neoplastic Diseases
5.8. Monitoring of Effects During Cancer Prevention and Immunotherapy
5.8.1. Delayed Hypersensitivity Skin Test
5.8.2. Activity of Cytolytic T-lymphocytes In Vitro
5.8.3. Levels of Tumor Specific Antigens
5.8.4. Computed Tomographic (CT) Scan
5.8.5. Measurement of Putative Biomarkers
5.8.6. Sonogram
6. EXAMPLE
Administration of Hsp-Peptide Complexes in two UV-Induced Carcinoma Models in Mice
6.1 Prevention Modality
6.2 Treatment Modality
6.3 Measuring Generation of MHC Class I Restricted CD8+ CTLs Provides an Assay for In Vivo Tumor Rejection
6.4 GP96-Peptide Complexes Elicit a Memory T Cell Response
7. EXAMPLE
Administration of Hsp-Peptide Complexes in the Treatment of Hepatocellular Carcinoma
8. EXAMPLE
Administration of Hsp-Peptide Complexes in the Treatment of Colorectal Cancer
9. EXAMPLE
Method for Rapid Purification of Peptide-Associated Hsp70
9.1 Method and Results
1. INTRODUCTION
The present invention relates to methods and compositions for the prevention and treatment of infectious diseases, primary and metastatic neoplastic diseases, including, but not limited to human sarcomas and carcinomas. In the practice of the prevention and treatment of infectious diseases and cancer, compositions of complexes of heat is shock/stress proteins (hsps) including, but not limited to, hsp70, hsp90, gp96 alone or in combination with each other, noncovalently bound to antigenic molecules, are used to augment the immune response to genotoxic and nongenotoxic factors, tumors and infectious agents.
2. BACKGROUND OF THE INVENTION
The era of tumor immunology began with experiments by Prehn and Main, who showed that antigens on the methylcholanthrene (MCA)-induced sarcomas were tumor specific in that transplantation assays could not detect these antigens in normal tissue of the mice (Prehn, R. T., et al., 1957,
J. Natl. Cancer Inst.
1:769-778). This notion was confirmed by further experiments demonstrating that tumor specific resistance against MCA-induced tumors can be elicited in the autochthonous host, that is, the mouse in which the tumor originated (Klein, G., et al., 1960,
Cancer Res.
20:1561-1572).
In subsequent studies, tumor specific antigens were also found on tumors induced with other chemical or physical carcinogens or on spontaneous tumors (Kripke, M. L., 1974,
J. Natl. Cancer Inst.
53:1333-1336; Vaage, J., 1968,
Cancer Res.
28:2477-2483; Carswell, E. A., et al., 1970,
J. Natl. Cancer Inst.
44:1281-1288). Since these studies used protective immunity against the growth of transplanted tumors as the criterion for tumor specific antigens, these antigens are also commonly referred to as “tumor specific transplantation antigens” or “tumor specific rejection antigens.” Several factors can greatly influence the immunogenicity of the tumor induced, including, for example, the specific type of carcinogen involved, immunocompetence of the host and latency period (Old, L. J., et al., 1962,
Ann. N.Y. Acad. Sci.
101:80-106; Bartlett, G. L., 1972,
J. Natl. Cancer Inst.
49:493-504).
Most, if not all, carcinogens are mutagens which may cause mutation, leading to the expression of tumor specific antigens (Ames, B. N., 1979,
Science
20:587-593; Weisburger, J. H., et al., 1981,
Science
21:401-407). Some carcinogens are immunosuppressive (Malmgren, R. A., et al., 1952,
Proc. Soc. Exp. Biol. Med.
79:484-488). Experimental evidence suggests that there is a constant inverse correlation between immunogenicity of a tumor and latency period (time between exposure to carcinogen and tumor appearance) (Old, L. J., et al., 1962,
Ann. N.Y. Acad. Sci.
101:80-106; and Bartlett, G. L., 1972,
J. Natl. Cancer Inst.
49:493-504). Other studies have revealed the existence of tumor specific antigens that do not lead to rejection, but, nevertheless, can potentially stimulate specific immune responses (Roitt, I., Brostoff, J and Male, D., 1993, Immunology, 3rd ed., Mosby, St. Louis, pps. 17.1-17.12).
2.1. Tumor-Specific Immunogenicities of Heat Shock/Stress Proteins hsp70. hsp90 and gp96
Srivastava et al. demonstrated immune response to methylcholanthrene-induced sarcomas of inbred mice (1988,
Immunol. Today
9:78-83). In these studies it was found that the molecules responsible for the individually distinct immunogenicity of these tumors were identified as cell-surface glycoproteins of 96 kDa (gp96) and intracellular proteins of 84 to 86 kDa (Srivastava, P. K., et al., 1986,
Proc. Natl. Acad. Sci. USA
83:3407-3411; Ullrich, S. J., et al., 1986,
Proc. Natl. Acad. Sci. USA
83:3121-3125. Immunization of mice with gp96 or p84/86 isolated from a particular tumor rendered the mice immune to that particular tumor, but not to antigenically distinct tumors. Isolation and characterization of genes encoding gp96 and p84/86 revealed significant homology between them, and showed that gp96 and p84/86 were, respectively, the endoplasmic reticular and cytosolic counterparts of the same heat shock proteins (Srivastava, P. K., et al., 1988,
Immunogenetics
28:205-207; Srivastava, P. K., et al., 1991,
Curr. Top. Microbiol. Immunol.
167:109-123). Further, hsp70 was shown to elicit immunity to the tumor from which it was isolated but not to antigenically distinct tumors. However, hsp7o depleted of peptides was found to lose its immunogenic activity (Udono, M., and Srivastava, P. K., 1993,
J. Exp. Med.
1:1391-1396). These observations suggested that the heat shock proteins are not immunogenic per se, but are carriers of antigenic peptides that elicit specific immunity to cancers (Srivastava, P. K., 1993,
Adv. Cancer Res.
62:153-177).
2.2. Pathobiology of Cancer
Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, and lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis). Clinical data and molecular biologic studies indicate that cancer is a multistep process that begins with minor preneoplastic changes, which may under certain conditions progress to neoplasia.
Pre-malignant abnormal cell growth is exemplified by hyperplasia, metaplasia, or most particularly, dysplasia (for review of such abnormal growth conditions, see Robbins and Angell, 1976,
Basic Pathology,
2d Ed., W. B. Saunders Co., Philadelphia, pp. 68-79.) Hyperplasia is a form of controlled cell proliferation involving an increase in cell number in a tissue or organ, without significant alteration in structure or function. As but one example, endometrial hyperplasia often precedes endometrial cancer. Metaplasia is a form of controlled cell growth in which one type of adult or fully
Bansal Geetha P.
Fordham University
Pennie & Edmonds LLP
LandOfFree
Compositions and methods using complexes of heat shock... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions and methods using complexes of heat shock..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions and methods using complexes of heat shock... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2609257