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Effect Of Human Natural Killer and T Cells on the Growth of Human Autologous Melanoma Xenografts in SCID Mice

¹Laboratories of Immunology and ²Virology, Istituto Superiore di Sanità, Rome; ³Istituto Nazionale per la Ricerca sul Cancro, Genova; ⁴Fondazione "A. Cesalpino," Dipartimento Medicina Interna, Università La Sapienza, Rome; ⁵Unit of Immunotherapy of Human Tumors, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan; ⁶Istituto Giannina Gaslini, Genova; and ⁷Dipartimento di Medicina Sperimentale and ⁸Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genova, Italy

Natural killer (NK) cells were first identified for their ability to kill tumor cells of different origin in vitro. Similarly, T lymphocytes display strong cytotoxic activity against various tumor cell lines. However, the ability of both the NK and cells to mediate natural immune response against human malignant tumors in vivo is still poorly defined. Severe combined immunodeficient (SCID) mice have been successfully engrafted with human tumors. In this study, the antitumor effect of local as well as of systemic treatments based on NK cells or V1 or V2 / T lymphocytes against autologous melanoma cells was investigated in vivo. The results show that all three of the populations were effective in preventing growth of autologous human melanomas when both tumor and lymphoid cells were s.c. inoculated at the same site. However, when lymphoid cells were infused i.v., only NK cells and V1 / T lymphocytes could either prevent or inhibit the s.c. growth of autologous melanoma. Accordingly, both NK cells and V1 T lymphocytes could be detected at the s.c. tumor site. In contrast, V2 T lymphocytes were only detectable in the spleen of the SCID mice. Moreover, NK cells maintained their inhibitory effect on tumor growth even after discontinuation of the treatment. Indeed they were present at the tumor site for a longer period.

These data support the possibility to exploit NK cells and V1 T lymphocytes in tumor immunotherapy. Moreover, our study emphasizes the usefulness of human tumor/SCID mouse models for preclinical evaluation of immunotherapy protocols against human tumors.

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