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Cancer Immunology, Immunotherapy

, Volume 36, Issue 3, pp 156–162 | Cite as

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

  • Steven M. Dubinett
  • Lisa Patrone
  • Jeffery Tobias
  • Alistair J. Cochran
  • Duan-Ren Wen
  • William H. McBride
Original articles

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.

Key words

Interleukin-2 Immunotherapy Tumorinfiltrating lymphocytes 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Steven M. Dubinett
    • 1
    • 2
    • 6
  • Lisa Patrone
    • 2
  • Jeffery Tobias
    • 2
  • Alistair J. Cochran
    • 3
    • 4
  • Duan-Ren Wen
    • 3
    • 4
  • William H. McBride
    • 5
    • 6
  1. 1.Department of Medicine, Division of Pulmonary and Critical Care MedicineUCLA School of Medicine, Wadsworth VALos AngelesUSA
  2. 2.Medical Research ServiceWadsworth Veterans Administration Medical CenterLos AngelesUSA
  3. 3.Department of Pathology and Laboratory MedicineUCLA School of MedicineLos AngelesUSA
  4. 4.Department of SurgeryUCLA School of MedicineLos AngelesUSA
  5. 5.Department of Radiation OncologyUCLA School of MedicineLos AngelesUSA
  6. 6.Jonsson Comprehensive Cancer CenterUCLA School of MedicineLos AngelesUSA

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