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CTL-Dependent and -Independent Antitumor Immunity Is Determined by the Tumor Not the Vaccine¹

Jaina Leitch^*, Katie Fraser^*, Cecilia Lane^*, Kelley Putzu^*, Gosse J. Adema, Qian-Jin Zhang, Wilfred A. Jefferies, Jonathan L. Bramson^* and Yonghong Wan^2,*

^* Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Tumor Immunology Laboratory, University Medical Center Nijmegen, St. Radboud, Nijmegen, The Netherlands; and Biotechnology Laboratory, Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

Previously, we compared the efficiency of direct injection with an adenovirus (Ad) expressing human gp100 (hgp100) to immunization with dendritic cells (DC) loaded with the same vector ex vivo. The DC vaccine provided the greatest protection against challenge with B16F10 melanoma, and antitumor immunity was found to be CD8⁺ T cell-independent. In the current study, we sought to determine whether lack of CD8⁺ T cell-mediated antitumor immunity was a function of the vaccine platform or the tumor line. Both Ad and DC/Ad vaccines elicited CD8⁺ CTL reactive against hgp100 and provided protection against B16F10 engineered to express hgp100 demonstrating that both vaccination platforms can effectively generate protective CD8⁺ T cell-mediated immunity. The hgp100-induced CTL cross-reacted with murine gp100 (mgp100) and lysed B16F10 cells pulsed with mgp100 peptide indicating that the resistance of B16F10 cells to CTL elicited by hgp100 vaccination may be due to a defect in processing of the endogenous mgp100. Indeed, introduction of the TAP-1 cDNA into B16F10 rendered the cells sensitive to lysis by gp100-specific CTL. Furthermore, gp100-immunized mice were protected from challenge with B16F10-TAP1 cells through a mechanism dependent upon CD8⁺ T cells. These results demonstrate that tumor phenotype, not the vaccination platform, ultimately determines CD8⁺ or CD4⁺ T cell-mediated tumor clearance.

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