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[Cancer Research 61, 8105-8109, November 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Comparative Analysis of Necrotic and Apoptotic Tumor Cells As a Source of Antigen(s) in Dendritic Cell-based Immunization1

Yoshihito Kotera, Koichi Shimizu2 and James J. Mulé3

Departments of Surgery [Y. K., K. S., J. J. M.] and Internal Medicine [J. J. M.], and the Tumor Immunology and Immunotherapy Program of the Comprehensive Cancer Center [Y. K., K. S., J. J. M.], University of Michigan Medical Center, Ann Arbor, Michigan, 48109-0666

There is considerable controversy as to whether necrotic (lysate) or apoptotic tumor cells serve as the superior source of multiple tumor-associated antigens (TAAs) to pulse dendritic cells (DCs) for immunotherapeutic applications. Here, we show that standard procedures to induce apoptosis by UVB irradiation unequivocally result in a mixed population of viable, apoptotic, and necrotic tumor cells, necessitating additional purification. We used highly enriched apoptotic versus lysate of B16 melanoma cells to examine whether or not there are important distinctions between these two sources of TAAs for loading of DCs. Our results demonstrate that although some differences exist between the two forms of TAAs in expression of heat shock proteins, as well as production of interleukin-12 by pulsed DCs, their respective capacities to mature DCs phenotypically, as well as to elicit both effective immune priming and antitumor therapeutic efficacy in vivo when presented by DCs, are equivalent.




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