BIODEGRADABLE MICROSPHERES FOR CANCER IMMUNOTHERAPY

DESCRIPTION: A novel technology for the local and sustained delivery of immunostimulatory molecules to the tumor environment for cancer immunotherapy is evaluated. The ability of biodegradable polymer micro spheres loaded with murine Interleukin- 12 to promote the regression of established tumors and distant metastatic lesions is investigated in a syngeneic murine tumor model. The feasibility of this new sustained delivery system has ahead been established by demonstrating that different cytokines can be loaded into and released from the micro spheres in a biologically active form both in vitro and in vivo. Our objective here is to test our patent-protected cytokine-loaded micro spheres for their ability to deliver cytokines to established tumors and thereby eliminate tumors and provoke an antitumor immunity. In Aim 1, intralesional injections of IL-12- loaded micro spheres are employed to induce the suppression and/or regression of established primary tumors with the concomitant development of protective antitumor immunity. In Aim 2, the protocols that are found to be effective in Aim 1 are tested for their ability to promote the suppression of established lung metastases in a clinically relevant spontaneous metastasis model. The results from these Phase I studies are expected to establish whether cytokine-loaded micro spheres represent a simpler, more versatile and clinically feasible alternative to gene-modified tumor cell vaccines for adjuvant cytokine immunotherapy of cancer. PROPOSED COMMERCIAL APPLICATION: If proven effective, our tumor vaccination approach involving cytokine-loaded microspheres will provide a simple and universally applicable alternative to cumbersome and very expensive cytokine gene therapy strategies that are currently being tested in human clinical trials. This treatment has the potential to become a widely utilized adjuvant therapy to current standard treatments for cancer.