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Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Cancer vaccines can induce the in vivo generation of tumor Ag-specific T cells in patients with metastatic melanoma yet seldom elicit objective clinical responses. Alternatively, adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in 50% of lymphodepleted patients, but are logistically and technically difficult to generate. In this study, we evaluated the capability of vaccine-induced PBMC to mediate tumor regression after transfer to patients receiving the same chemotherapy-induced lymphodepletion used for TIL transfer therapy. Autologous PBMC from nine gp100-vaccinated patients with metastatic melanoma were stimulated ex vivo with the gp100:209–217(210M) peptide and transferred in combination with high-dose IL-2 and cancer vaccine. Transferred PBMC contained highly avid, gp100:209–217 peptide-reactive CD8+ T cells. One week after transfer, lymphocyte counts peaked (median of 14.3 x 103 cells/µl; range of 0.9–59.7 x 103 cells/µl), with 56% of patients experiencing a lymphocytosis. gp100:209–217 peptide-specific CD8+ T cells persisted at high levels in the blood of all patients and demonstrated significant tumor-specific IFN-
secretion in vitro. Melanocyte-directed autoimmunity was noted in two patients; however, no patient experienced an objective clinical response. These studies demonstrate the feasibility and safety of using vaccine-induced PBMC for cell transfer, but suggests that they are not as effective as TIL in adoptive immunotherapy even when transferred into lymphodepleted hosts.
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, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.
2 Address correspondence and reprint requests to Dr. Daniel J. Powell, Jr., Surgery Branch, National Cancer Institute, National Institutes of Health, CRC Room 3W-3888, 10 Center Drive, Bethesda, MD 20892. E-mail address: Daniel_Powell{at}nih.gov
3 Abbreviations used in this paper: TIL, tumor-infiltrating lymphocyte; ACT, adoptive cell transfer; CM, complete medium; TRBV, TCR
-chain V region; Treg, regulatory T; ALC, absolute lymphocyte count; IHC, immunohistochemical.
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