Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B-cell lymphoma in vivo.
The in vitro priming of tumor-specific T cells by dendritic cells (DCs) phagocytosing killed tumor cells can be augmented in the presence of antitumor monoclonal antibody (mAb). We investigated whether DCs phagocytosing killed lymphoma cells coated with tumor-specific antibody could elicit antitumor immunity in vivo. Irradiated murine 38C13 lymphoma cells were cocultured with bone marrow-derived DCs in the presence or absence of tumor-specific mAb. Mice vaccinated with DCs cocultured 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 preexisting 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 antilymphoma immunity might be achieved by combining these approaches.
Franki
Suzanne N
SN
Division of Hematology and Oncology, Department of Medicine, University of California Los Angeles, LA, CA 90095-1678, USA.
Steward
Kristopher K
KK
Betting
David J
DJ
Kafi
Kamran
K
Yamada
Reiko E
RE
Timmerman
John M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005260:Female; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D010586:Phagocytes / Q000276:immunology / Q000528:radiation effects; D012680:Sensitivity and Specificity; D013154:Spleen / Q000276:immunology; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007130:Immunoglobulin Idiotypes