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, Avi Markowitz, A. C. Von Eschenbach, S. S. Legha, C. M. Balch, M. I. Ross, L. B. Augustus, K. Itoh

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    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 CD3-CD56+ NK cells with major histocompatibility complex-nonrestricted 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 CD3-CD56+ 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 CD3-CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN)-γ, while nonadherent TIL did not. These results suggest that initially cytotoxic CD3-CD56+ 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. Three 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
    StatePublished - 1991

    Fingerprint

    Tumor-Infiltrating Lymphocytes
    Natural Killer T-Cells
    Renal Cell Carcinoma
    Melanoma
    Natural Killer Cells
    Therapeutics
    T-Lymphocytes
    Interleukin-2
    Interferons
    Serum-Free Culture Media
    Cytotoxic T-Lymphocytes
    Major Histocompatibility Complex
    Cyclophosphamide

    Keywords

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

    ASJC Scopus subject areas

    • Cancer Research
    • Immunology
    • Pharmacology

    Cite this

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

    In: Journal of Immunotherapy, Vol. 10, No. 5, 1991, p. 313-325.

    Research output: Contribution to journalArticle

    Hayakawa, K, Salmeron, MA, Parkinson, DR, Markowitz, A, Von Eschenbach, AC, Legha, SS, Balch, CM, Ross, MI, Augustus, LB & 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, vol. 10, no. 5, pp. 313-325.
    Hayakawa, K. ; Salmeron, M. A. ; Parkinson, D. R. ; Markowitz, Avi ; Von Eschenbach, A. C. ; Legha, S. S. ; Balch, C. M. ; Ross, M. I. ; Augustus, L. B. ; Itoh, K. / 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. In: Journal of Immunotherapy. 1991 ; Vol. 10, No. 5. pp. 313-325.
    @article{03a3826555a14a7b808f986071869a4c,
    title = "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",
    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 CD3-CD56+ NK cells with major histocompatibility complex-nonrestricted 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 CD3-CD56+ 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 CD3-CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN)-γ, while nonadherent TIL did not. These results suggest that initially cytotoxic CD3-CD56+ 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. Three cytotoxic melanoma TIL were adoptively transferred to melanoma patients. Three of seven RCC patients responded to the adoptive therapy.",
    keywords = "Adoptive cellular therapy, Interleukin-2, Metastatic melanoma, Renal cell carcinoma, Tumor-infiltrating lymphocytes",
    author = "K. Hayakawa and Salmeron, {M. A.} and Parkinson, {D. R.} and Avi Markowitz and {Von Eschenbach}, {A. C.} and Legha, {S. S.} and Balch, {C. M.} and Ross, {M. I.} and Augustus, {L. B.} and K. Itoh",
    year = "1991",
    language = "English (US)",
    volume = "10",
    pages = "313--325",
    journal = "Journal of Immunotherapy",
    issn = "1524-9557",
    publisher = "Lippincott Williams and Wilkins",
    number = "5",

    }

    TY - JOUR

    T1 - Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma

    T2 - Sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC

    AU - Hayakawa, K.

    AU - Salmeron, M. A.

    AU - Parkinson, D. R.

    AU - Markowitz, Avi

    AU - Von Eschenbach, A. C.

    AU - Legha, S. S.

    AU - Balch, C. M.

    AU - Ross, M. I.

    AU - Augustus, L. B.

    AU - Itoh, K.

    PY - 1991

    Y1 - 1991

    N2 - 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 CD3-CD56+ NK cells with major histocompatibility complex-nonrestricted 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 CD3-CD56+ 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 CD3-CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN)-γ, while nonadherent TIL did not. These results suggest that initially cytotoxic CD3-CD56+ 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. Three cytotoxic melanoma TIL were adoptively transferred to melanoma patients. Three of seven RCC patients responded to the adoptive therapy.

    AB - 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 CD3-CD56+ NK cells with major histocompatibility complex-nonrestricted 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 CD3-CD56+ 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 CD3-CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN)-γ, while nonadherent TIL did not. These results suggest that initially cytotoxic CD3-CD56+ 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. Three cytotoxic melanoma TIL were adoptively transferred to melanoma patients. Three of seven RCC patients responded to the adoptive therapy.

    KW - Adoptive cellular therapy

    KW - Interleukin-2

    KW - Metastatic melanoma

    KW - Renal cell carcinoma

    KW - Tumor-infiltrating lymphocytes

    UR - http://www.scopus.com/inward/record.url?scp=0025952572&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0025952572&partnerID=8YFLogxK

    M3 - Article

    C2 - 1790139

    AN - SCOPUS:0025952572

    VL - 10

    SP - 313

    EP - 325

    JO - Journal of Immunotherapy

    JF - Journal of Immunotherapy

    SN - 1524-9557

    IS - 5

    ER -