This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Crowley, N. J. Articles by Seigler, H. F. Search for Related Content PubMed PubMed Citation Articles by Crowley, N. J. Articles by Seigler, H. F.

Human Xenograft-Nude Mouse Model of Adoptive Immunotherapy with Human Melanoma-specific Cytotoxic T-Cells¹

Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710

We investigated the efficacy of human melanoma-specific cytotoxic T-cells (CTLs) in treating experimental human melanoma metastases in a nude mouse model of adoptive immunotherapy. Hepatic metastases were generated by the intrasplenic injection of 1.5 x 10⁶ human melanoma cells. Animals were then randomized to receive saline, interleukin-2 only, or CTLs and interleukin-2. CTLs were effective when administered 3 or 7 days after generation of hepatic metastases, with 96 and 88% of animals disease-free, respectively, when examined at one month. Interleukin-2 alone was not effective. In addition, CTLs were effective when as few as 2.5 x 10⁶ T-cells were adoptively transferred. Only 33% of the animals were tumor-free when CTLs were administered on day 10, and CTLs were not effective when given at day 14. Human CTLs that were not cytotoxic for the tumor line used in vivo, when tested in a ⁵¹Cr assay, were also not effective in the model of immunotherapy. This suggests that the tumor-specific CTLs maintain their specificity in vivo, and eliminates a nonspecific inflammation directed against the human CTLs as a possible cause of the antitumor effect. These studies lay the foundation for clinical trials of CTLs in the adoptive immunotherapy of patients with metastatic melanoma.

¹ This work was supported in part by NIH Grant 2-PO1-CA-32672-05A1, Veterans Administration Project 821, and the DuPont Corporation, Wilmington, DE.

² To whom requests for reprints should be addressed, at: Department of Surgery, Box 3279, Duke University Medical Center, Durham, NC 27710.

Received 7/26/91. Accepted 10/29/91.

This article has been cited by other articles:

				J. Lin, L. Lin, D. G. Thomas, J. K. Greenson, T. J. Giordano, G. S. Robinson, R. A. Barve, F. A. Weishaar, J. M. G. Taylor, M. B. Orringer, et al. Melanoma-Associated Antigens in Esophageal Adenocarcinoma: Identification of Novel MAGE-A10 Splice Variants Clin. Cancer Res., September 1, 2004; 10(17): 5708 - 5716. [Abstract] [Full Text] [PDF]

				N. C. V. Verra, A. Jorritsma, K. Weijer, J. J. Ruizendaal, A. Voordouw, P. Weder, E. Hooijberg, T. N. M. Schumacher, J. B. A. G. Haanen, H. Spits, et al. Human Telomerase Reverse Transcriptase-Transduced Human Cytotoxic T Cells Suppress the Growth of Human Melanoma in Immunodeficient Mice Cancer Res., March 15, 2004; 64(6): 2153 - 2161. [Abstract] [Full Text] [PDF]

				N. J. Crowley and H. F. Seigler Relationship Between Disease-Free Interval and Survival in Patients With Recurrent Melanoma Arch Surg, November 1, 1992; 127(11): 1303 - 1308. [Abstract] [PDF]