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 signalling in tumor associated macrophages.
Infiltration of CD8+ T cells (red) into tumor nests after vaccination