Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma: Sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC

K. Hayakawa, M. A. Salmeron, D. R. Parkinson, A. B. Markowitz, A. C. Von Eschenbach, S. S. Legha, C. M. Balch, M. I. Ross, L. B. Augustus, K. Itoh

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    23 Scopus citations

    Abstract

    We investigated the immunological properties of interleukin-2 (IL- 2)-activated tumor-infiltrating lymphocytes (TIL), which were used for adoptive therapy of renal cell carcinoma (RCC) (seven patients) by focusing on natural killer (NK) cells, and metastatic melanoma (six patients) by focusing on cytotoxic T lymphocytes. TIL from five of seven cases proliferated well in culture with AIM-V serum-free medium and 1000 U/ml rIL-2 in 3-L gas permeable bags, whereas TIL from two RCCs exhibited delayed proliferation. Proliferation of CD3CD56+ NK cells with major histocompatibility complexnonrestricted cytotoxicity in RCC-TIL (n=6, mean=651-fold, ranging from 39- to 3450-fold) for the first 2-4 weeks was 63 times higher than that of noncytotoxic CD3+ T cells (n=6, 10.3-fold ranging from 0.8 to 35-fold). Thereafter, CD3+ T cells predominantly proliferated, and proliferation of CD3+ T cells (n=5, 743-fold) for 5-6 weeks were 24 times higher than that of CD3CD56+ NK cells (n=5, 31-fold). Significant numbers of RCC-TIL became adherent to the surfaces of the bags several weeks after initiation of culture. These adherent TIL consisted of more CD3CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN), while nonadherent TIL did not. These results suggest that initially cytotoxic CD3CD56 + NK cells and, later, noncytotoxic CD3+ T cells proliferated in culture of RCC-TIL for adoptive therapy. These noncytotoxic TIL were primarily transferred to RCC patients, who also received cyclophosphamide, IL-2, and IFN-α. In contrast to RCC-TIL, IL-2- activated melanoma TIL consisting of all CD3 + T cells displayed modest levels of cytotoxicity, primarily restricted to autologous melanoma cells in all cases tested. The cytotoxic melanoma TIL were adoptively transferred to melanoma patients. Three of seven RCC patients responded to the adoptive therapy.

    Original languageEnglish (US)
    Pages (from-to)313-325
    Number of pages13
    JournalJournal of Immunotherapy
    Volume10
    Issue number5
    DOIs
    StatePublished - Oct 1991

    Keywords

    • Adoptive cellular therapy
    • Interleukin-2
    • Metastatic melanoma
    • Renal cell carcinoma
    • Tumor-infiltrating lymphocytes

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Pharmacology
    • Cancer Research

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  • Cite this

    Hayakawa, K., Salmeron, M. A., Parkinson, D. R., Markowitz, A. B., Von Eschenbach, A. C., Legha, S. S., Balch, C. M., Ross, M. I., Augustus, L. B., & Itoh, K. (1991). Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma: Sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC. Journal of Immunotherapy, 10(5), 313-325. https://doi.org/10.1097/00002371-199110000-00003