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Baculovirus-Infected Insect Cells Expressing Peptide-MHC Complexes Elicit Protective Antitumor Immunity¹

Kimberly R. Jordan^*, Rachel H. McMahan^*, Jason Z. Oh^*, Matthew R. Pipeling, Drew M. Pardoll, Ross M. Kedl^*, John W. Kappler^*,, and Jill E. Slansky^2,*

^* University of Colorado Denver and Health Sciences Center, Denver, CO 80206; Johns Hopkins University, Sidney Kimmel Cancer Center, Baltimore, MD 21231; National Jewish Medical and Research Center, Denver, CO 80206; and Howard Hughes Medical Institute, Denver, CO 80206

Evaluation of T cell responses to tumor- and pathogen-derived peptides in preclinical models is necessary to define the characteristics of efficacious peptide vaccines. We show in this study that vaccination with insect cells infected with baculoviruses expressing MHC class I linked to tumor peptide mimotopes results in expansion of functional peptide-specific CD8⁺ T cells that protect mice from tumor challenge. Specific peptide mimotopes selected from peptide-MHC libraries encoded by baculoviruses can be tested using this vaccine approach. Unlike other vaccine strategies, this vaccine has the following advantages: peptides that are difficult to solublize can be easily characterized, bona fide peptides without synthesis artifacts are presented, and additional adjuvants are not required to generate peptide-specific responses. Priming of antitumor responses occurs within 3 days of vaccination and is optimal 1 wk after a second injection. After vaccination, the Ag-specific T cell response is similar in animals primed with either soluble or membrane-bound Ag, and CD11c⁺ dendritic cells increase expression of maturation markers and stimulate proliferation of specific T cells ex vivo. Thus, the mechanism of Ag presentation induced by this vaccine is consistent with cross-priming by dendritic cells. This straightforward approach will facilitate future analyses of T cells elicited by peptide mimotopes.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Cancer Institute Grant CA109560 and a seed grant from the American Cancer Society Institutional Research grant to the University of Colorado Cancer Center (to J.E.S.). K.R.J., R.H.M., and J.Z.O. were supported in part by the Cancer Research Institute Predoctoral Emphasis Pathway in Tumor Immunology Fellowship.

² Address correspondence and reprint requests to Dr. Jill E. Slansky, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail address: jill.slansky{at}uchsc.edu

³ Abbreviations used in this paper: BV, baculovirus; β-gal, β-galactosidase; β₂m, β₂-microglobulin; CT, colorectal tumor; DC, dendritic cell; MFI, mean fluorescence intensity; Sf9, Spodoptera frugiperda; Tg, transgenic.