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Intratumoral interleukin-2 immunotherapy: Activation of tumor-infiltrating and splenic lymphocytes in vivo

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Abstract

Direct intratumoral injection of interleukin-2 (IL-2) was evaluated in a murine model. Balb/c mice received 5 × 104 Line 1 alveolar carcinoma cells (L1C2) by subcutaneous injection. On the third day following tumor implantation, mice received injections of IL-2 (5 × 103−5 × 104 units) or diluent twice daily, either by i. p. or intratumoral injection, 5 days/week for 3 weeks. Intratumoral injection of 5 × 104 units IL-2 significantly reduced tumor volume (P <0.05 versus control), increased median survival time (P = 0.0001), and resulted in a 23.5% cure rate (P = 0.008). There were no long-term survivors in the other treatment groups. Both tumor-infiltrating lymphocytes (TIL) and splenic lymphocytes isolated directly from IL-2-treated mice demonstrated enhanced cytolytic activity compared to diluent-treated controls. To determine whether non-T-cell-mediated antitumor responses were active in our model, intratumoral immunotherapy was evaluated in athymic Balb/cnu/nu mice. In order to decrease the recruitment of lymphocyte precursors, nude mice were splenectomized and received cyclophosphamide prior to tumor injection and IL-2 therapy. Intratumoral IL-2 immunotherapy also significantly decreased tumor volume in these immunodeficient mice (P <0.02), but did not lead to long-term survival. We conclude that both TIL and splenic lymphocytes are activated in vivo in response to intratumoral IL-2 immunotherapy, suggesting that intratumoral therapy with IL-2 activates both local and systemic antitumor responses.

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Authors and Affiliations

  1. Department of Medicine, Division of Pulmonary and Critical Care Medicine, UCLA School of Medicine, Wadsworth VA, W111B, Wilshire and Sawtelle Blvds., 90 073, Los Angeles, California, USA

    Steven M. Dubinett

  2. Medical Research Service, Wadsworth Veterans Administration Medical Center, Los Angeles, CA, USA

    Steven M. Dubinett, Lisa Patrone & Jeffery Tobias

  3. Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, USA

    Alistair J. Cochran & Duan-Ren Wen

  4. Department of Surgery, UCLA School of Medicine, Los Angeles, USA

    Alistair J. Cochran & Duan-Ren Wen

  5. Department of Radiation Oncology, UCLA School of Medicine, Los Angeles, USA

    William H. McBride

  6. Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California, USA

    Steven M. Dubinett & William H. McBride

Authors
  1. Steven M. Dubinett
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  2. Lisa Patrone
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  3. Jeffery Tobias
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  4. Alistair J. Cochran
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  5. Duan-Ren Wen
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  6. William H. McBride
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Supported by the Tobacco-Related Disease Research Program of the University of California, the Cancer Research Coordinating Committee, the Jonsson Cancer Center Foundation, and Veterans Administration Medical Research Funds

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Dubinett, S.M., Patrone, L., Tobias, J. et al. Intratumoral interleukin-2 immunotherapy: Activation of tumor-infiltrating and splenic lymphocytes in vivo. Cancer Immunol Immunother 36, 156–162 (1993). https://doi.org/10.1007/BF01741086

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  • DOI: https://doi.org/10.1007/BF01741086

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