The proposed studies will focus on developing an immunological approach for breast cancer gene therapy that results in regression of primary tumors and residual metastatic foci and induces sufficient immunological memory to prevent tumor recurrence and progression.
The studies are based upon Agracetus¿ previous findings that particle-mediated transfer of IL-12 gene in vivo can (1) cause complete regression of established malignant tumors, (2) eradicate tumor metastases, and (3) induce sufficient immunological memory to prevent future tumor growth. Thus, the proposed studies are highly relevant to breast cancer treatment.
Experiments will be performed to (1) elicit antitumor immunity by particle-mediated delivery of IL-12 gene in vivo, (2) analyze the specific and nonspecific immune mechanisms of antitumor activities induced by IL-12 gene therapy, and (3) suppress or eradicate spontaneous micrometastases of mammary tumors by activating systematic antitumor immunity via IL-12 gene therapy.
These studies should provide data required to support a clinical trial of gene gun-mediated IL-12 gene therapy for breast cancers and to aid other groups investigating (1) tumor immunotherapies against other forms of cancer, (2) cytokines as adjuvants in vaccines against various infectious diseases--including biological defense targets, and (3) immunological therapeutics against harmful microbes and toxins. |