Submitted March 19, 2007
Accepted November 2, 2007
Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B cell lymphoma in vivo
Suzanne N Franki, Kristopher K Steward, David J Betting, Kamran Kafi, Reiko E Yamada, and John M Timmerman*
Division of Hematology & Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, United States
Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, United States
* Corresponding author; email: jtimmerman{at}mednet.ucla.edu.
The in vitro priming of tumor-specific T cells by dendritic cells (DCs) phagocytosing killed tumor cells can be augmented in the presence of anti-tumor monoclonal antibody (mAb). We investigated whether DCs phagocytosing killed lymphoma cells coated with tumor-specific antibody could elicit anti-tumor immunity in vivo. Irradiated murine 38C13 lymphoma cells were co-cultured with bone marrow-derived DCs in the presence or absence of tumor-specific mAb. Mice vaccinated with DCs co-cultured with mAb-coated tumor cells were protected from tumor challenge (60% long-term survival), whereas DCs loaded with tumor cells alone were much less effective. The opsonized whole tumor cell-DC vaccine elicited significantly better tumor protection than a traditional lymphoma idiotype (Id) protein vaccine, and in combination with chemotherapy could eradicate pre-existing tumor. Moreover, the DC vaccine protected animals from both wild-type and Id-negative variant tumor cells, indicating that Id is not a major target of the induced tumor immunity. Protection was critically-dependent upon CD8+ T cells, with lesser contribution by CD4+ T cells. Importantly, opsonized whole tumor cell-DC vaccination did not result in tissue-specific autoimmunity. Since opsonized whole tumor cell-DC and Id vaccines appear to target distinct tumor antigens, optimal anti-lymphoma immunity might be achieved by combining these approaches.
