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AGENCY USE ONLY (Leave blank)2. REPORT DATE
July 1999
REPORT TYPE AND DATES COVEREDAnnual Summary (1 Jul 98 -30 Jun 99)
TITLE AND SUBTITLEImmunotherapeutic Cell-Based Vaccine to Combat Metastatic Breast Cancer
AUTHOR(S)Pulaski, Beth A., Ph.D.
PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Maryland Baltimore County Baltimore, Maryland 21250 E*Mail: pulaski@umbc.edu
SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)U
ABSTRACT (Maximum 200 words)^0sl g m ticant improvements tor treatment of metastatic breast cancer have seen developed in the last 20 years and the prognosis for women with this disease remains poor. Progress n understanding the immune response, however, has led to renewed enthusiasm for immune-based anti ;ancer therapies. Previously, we demonstrated that tumor cell-based vaccines expressing MHC class II and 37.1 (CD80) molecules reduced experimental (i.v.-induced) and established spontaneous metastatic disease, ?y activating tumor-specific CD4 + T-lymphocytes. We now demonstrate, using the mouse 4T1 mammary carcinoma, that a novel immunotherapy consisting of the cytokine IL-12 and SEB superantigen combined vith the previously described cell-based vaccine produces an even greater reduction in spontaneous netastatic disease and significant extension of mean survival time in two distinct immunotherapeutic •egimens. The therapeutic effect is particularly noteworthy because: 1) spontaneous metastatic cancer by 1T1 progresses similarly in comparison to human metastatic mammary cancer, 2) our post-operative model iemonstrates that early metastatic lesions are primarily responsible for morbidity, 3) the metastatic disease s extensive prior to initiation of immunotherapy in both regimens, and 4) multiple effector cell populations including T and NK cells, and anti-angiostatic factors are likely to mediate the anti-tumor effect. In conducting research utilizing recombinant DNA technology, the investigator(s) adhered to current guidelines promulgated by the National Institutes of Health.
<#In the conduct of research utilizing recombinant DNA, the investigator(s) adhered to the NIH Guidelines for Research Involving Recombinant DNA Molecules.yk In the conduct of research involving hazardous organisms, the investigator(s) adhered to the CDC-NIH Guide for Biosafety in Microbiological and Biomedical Laboratories....