EFFICIENT TUMOR-ERADICATION BY ADOPTIVELY TRANSFERRED CYTOTOXIC T-CELL CLONES IN ALLOGENEIC HOSTS

Tumor-specific cytotoxic T cells (CTLs) can play an important role aga inst cancer as illustrated by the observation that adoptive transfer o f tumor-specific CTLs can mediate potent anti-tumor effects. Although such CTLs can be detected at the tumor site, relatively little is know n about the mechanisms by which they enter the tumor. In this study, t he role of major histocompatibility complex (MHC) class I molecules on vascular endothelium in the tumor in entry of, and tumor eradication by, tumor-specific CTL was investigated. Two H-2D(b)-restricted CTL cl ones recognizing peptide VNIRNCCYI on human adenovirus type 5 early re gion 1-(Ad5E1)-induced tumors were used to test whether CTLs were able to cross the vascular endothelium lacking the restricting MHC molecul e. One CTL clone recognizes peptide VNIRNCCYI in the context of both H -2D(b) and H-2D(bm14) molecules. The other CTL clone recognizes this p eptide only in the context of H-2D(b). Adoptive transfer of these CTLs leads to eradication of Ad5E1-induced, H-2D(b)-expressing tumors in B 6 (H-2D(b+)) and Bm14(H-2D(b-)) nude mice. Our data show that presenta tion of tumor-derived peptides by MHC molecules on endothelial cells o f blood vessels in a tumor do not play a major role in eradication of tumors by adoptively transferred CTL in combination with interleukin-2 . Moreover, our data show that successful adoptive CTL immunotherapy i s possible across allogeneic barriers, without inducing severe side ef fects, provided the tumor expresses the MHC class 1-peptide complex re cognized by the CTLs. (C) 1996 Wiley-Liss, Inc.