The immune system in cancer patients is often suppressed and attempts to apply immunotherapy are met with failure. We are proposing here to develop a new approach of experimental immunotherapy for cancer patients which is based on the idiotype network concept. According to this hypothesis, certain idiotopes mimick antigens (internal antigens), including self and tumor-associated antigens. Since we have recently used this concept to produce an experimental idiotope vaccines against streptococcal infection in mice, we will apply the same strategy to produce idiotope vaccines for cancer patients. Vaccination against streptococcal pneumonia is required in therapeutic protocols for lymphoproliferative malignancies; however existing vaccines (Pneumovax) often is ineffective. We propose to develop a substitute for this vaccine based on our experience with the anti-steptococcal idiotype vaccines in mice. We are also planning to develop an idiotope vaccine against human B cell lymphomas. This approach is based on our ability to produce specific hybridoma antibodies against lymphoproliferative malignancies which provide the necessary tools to generate anti-idiotypes expressing the internal antigens of such tumors. Finally, we will improve the compatibility and the effectiveness of murine-based idiotype vaccines by creating chiemiric mouse-man anti-idiotype antibodies using molecular biology methods.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA041636-03
Application #
3182357
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1986-04-01
Project End
1990-02-28
Budget Start
1988-09-01
Budget End
1990-02-28
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Bhattacharya-Chatterjee, M; Chatterjee, S K; Vasile, S et al. (1988) Idiotype vaccines against human T cell leukemia. II. Generation and characterization of a monoclonal idiotype cascade (Ab1, Ab2, and Ab3). J Immunol 141:1398-403
Huang, J Y; Ward, R E; Kohler, H (1988) Biological mimicry of antigenic stimulation: analysis of the in vivo antibody responses induced by monoclonal anti-idiotypic antibodies. Immunology 63:1-8
Kieber-Emmons, T; Ward, M M; Ward, R E et al. (1987) Structural considerations in idiotype vaccine design. Monogr Allergy 22:126-33
Bhattacharya-Chatterjee, M; Pride, M W; Seon, B K et al. (1987) Idiotype vaccines against human T cell acute lymphoblastic leukemia. I. Generation and characterization of biologically active monoclonal anti-idiotopes. J Immunol 139:1354-60
Kieber-Emmons, T; Getzoff, E; Kohler, H (1987) Perspectives on antigenicity and idiotypy. Int Rev Immunol 2:339-56
Sood, A K; Cheng, H L; Kohler, H (1986) An efficient and general method for sequencing immunoglobulin mRNAs. J Immunol Methods 95:227-35