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Departments of Surgery [T. M. M., X. L., E. A. P., J. D. I. E.] and Hematology [J-Y. S., D. J. D.], City of Hope National Medical Center, Duarte, California 91010
p53 gene mutations occur in most human cancers and result in an altered protein product that accumulates within the cell. Although the observed endogenous human CTL response to p53 is weak, high-affinity, human p53-specific CTLs have been generated from HLA A2.1 transgenic mice immunized with human CTL epitope peptides. In this study, we examine the ability of HLA A2.1-restricted and human p53-specific CTLs from HLA A2.1 transgenic mice to suppress the growth of p53-overexpressing human tumors in severe combined immunodeficient (SCID) mice. In vitro, murine p53149–157-specific CTLs selectively lysed the p53-overexpressing pancreatic carcinoma cell line Panc-1 but did not recognize HLA A2.1- tumor cells or HLA A2.1+ normal human fibroblasts. Furthermore, in vivo, the growth of established human tumor xenografts in SCID mice was significantly reduced and survival was prolonged after the administration of p53-specific CTLs but not after the administration of control CTLs or PBS alone. Following treatment with p53149–157-specific CTLs, regressing Panc-1 tumors were infiltrated by the CD8+ CTLs, as demonstrated by immunohistochemistry. These findings suggest that p53149–157-specific and HLA A2.1-restricted murine CTLs suppress the growth of established Panc-1 tumors following adoptive transfer into SCID hosts and prolong their survival.
1 This study was funded by American Cancer Society Fellowship Award 41797 (to T. M. M.) and United States Public Health Service Grants CA-70819 (to J. D. I. E.) and CA-30206 (to D. J. D.).
2 To whom requests for reprints should be addressed, at City of Hope National Medical Center, Department of General and Oncologic Surgery, 1500 East Duarte Road, Duarte, CA 91010. Phone: (626) 359-8111 ext. 3059; Fax: (626) 301-8865; E-mail: jellenhorn@smtplink.coh.org.
Received 12/19/97. Accepted 4/20/98.
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