Development of Cancer Vaccines
The identification of antigens associated with tumor destruction remains a major goal of cancer immunology. Vaccination with irradiated tumor cells engineered to secrete GM-CSF has been studied in Phase I clinical trials at Dana Farber/Harvard Cancer Care in malignant melanoma, NSCLC, ovarian cancer and sarcoma involving over 100 patients to date. Toxicities have been generally restricted to grade 1-2 local skin reactions, and several patients have had long-term (several years) disease-free intervals or have had stable disease. While at Dana-Farber, we conducted a Phase I clinical trial of autologous vaccination for patients with advanced breast cancer. Side effects due to the vaccines were limited and included skin site reactions, peripheral edema, and low-grade fevers. Immunologic assessment of vaccinated patients included multicolor flow cytometry, ELISPOT T cell analysis, and measurement of antibody responses using custom protein microarrays.
We are currently working on next-generation cancer vaccine development. This includes developing novel methods for in vitro tumor cell culture both for vaccine preparation and for ex vivo T cell expansion. We are also identifying in situ mechanisms that limit effective vaccine therapy, including dysregulation of the IL6/STAT3 signaling in tumor-associated macrophages.
Infiltration of CD8+ T cells (red) into tumor nests after vaccination