Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors

M. Z. Papa, J. C. Yang, J. T. Vetto, E. Shiloni, A. Eisenthal, S. A. Rosenberg

Research output: Contribution to journalArticle

Abstract

We have evaluated the effects of chemotherapeutic agents on the toxicity and antitumor benefit of therapy of established murine tumors by high-dose interleukin 2 (IL-2). Cyclophosphamide (Cy), doxorubicin, and bischloroethylnitrosourea were given to normal mice prior to IL-2 administration to test the effects of these agents on IL-2-induced toxicity. Cy at doses of 100 mg/kg and 150 mg/kg completely protected mice from a 100% lethal dose of IL-2, and doses of 50 mg/kg and 150 mg/kg allowed the administration of a median of 4.5 and 10.0 more doses of IL-2, respectively, before death from IL-2 toxicity occurred. Doxorubicin at 8 mg/kg and bischloroethylnitrosourea at 20 mg/kg did not impact on toxicity in IL-2 treated mice. In mice bearing pulmonary metastases of the weakly immunogenic MCA-105 sarcoma, IL-2 increased median survival time from 33 (no IL-2) to >60 days for all doses of IL-2 tested when combined with a single injection of Cy at 75 mg/kg (P <0.002). Increasing doses of either Cy or IL-2 produced increasing benefits on survival which were always greater than either treatment alone. These effects of Cy and IL-2 were also seen in mice bearing the nonimmunogenic MCA-101 sarcoma and a murine adenocarcinoma (MCA-38). Doxorubicin and bischloroethylnitrosourea did not consistently enhance the effects of IL-2 treatment. Cy appears to reduce the yield of in vivo generated lymphokine-activated killer cells, but these lymphokine-activated killer cells are still lytic for fresh tumor targets in vitro. Thus, the mechanism of the this synergy does not appear to involve stimulation of lymphokine-activated killer cell activity, but may in part involve reduction of tumor burden by the chemotherapeutic agent, an increase in susceptibility of tumor to cellular immune lysis, and/or a decrease in suppressor cell activity mediated by the chemotherapy.

Original languageEnglish (US)
Pages (from-to)122-129
Number of pages8
JournalCancer Research
Volume48
Issue number1
StatePublished - 1988
Externally publishedYes

Fingerprint

Interleukin-2
Drug Therapy
Lung
Cyclophosphamide
Neoplasms
Lymphokine-Activated Killer Cells
Therapeutics
Doxorubicin
Sarcoma
Tumor Burden
Adenocarcinoma
Neoplasm Metastasis
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Papa, M. Z., Yang, J. C., Vetto, J. T., Shiloni, E., Eisenthal, A., & Rosenberg, S. A. (1988). Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors. Cancer Research, 48(1), 122-129.

Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors. / Papa, M. Z.; Yang, J. C.; Vetto, J. T.; Shiloni, E.; Eisenthal, A.; Rosenberg, S. A.

In: Cancer Research, Vol. 48, No. 1, 1988, p. 122-129.

Research output: Contribution to journalArticle

Papa, MZ, Yang, JC, Vetto, JT, Shiloni, E, Eisenthal, A & Rosenberg, SA 1988, 'Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors', Cancer Research, vol. 48, no. 1, pp. 122-129.
Papa MZ, Yang JC, Vetto JT, Shiloni E, Eisenthal A, Rosenberg SA. Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors. Cancer Research. 1988;48(1):122-129.
Papa, M. Z. ; Yang, J. C. ; Vetto, J. T. ; Shiloni, E. ; Eisenthal, A. ; Rosenberg, S. A. / Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors. In: Cancer Research. 1988 ; Vol. 48, No. 1. pp. 122-129.
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