Importance in timing of cyclophosphamide on the enhancement of interleukin-2-induced cytolysis

Emmanuel Katsanis, Maria A. Bausero, Augusto C. Ochoa, Cynthia M. Loeffler, Bruce R. Blazar, Arnold S. Leonard, Peter M. Anderson

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

We investigated the in vivo effects of cyclophosphamide (CY) on interleukin-2(IL-2)-induced cytolytic function and spleen cell immunophenotype. Pretreatment of A/J mice with CY (25 mg/kg or 75 mg/kg) i.p. on days -10 and -15 followed by IL-2 (50 000 U i.p. on days 0 to +3) resulted in increased lysis of YAC-1 target cells compared to the group receiving IL-2 without previous CY therapy. In contrast, when CY was given on day -5, the cytotoxicity against YAC-1 was not enhanced. Phenotypic analysis of splenocytes obtained from mice treated with CY on day -10 or -15 revealed a relative decrease in L3T4- and Lyt2-positive T cells. In vivo depletion of natural killer (NK) cells by anti-asialoGM1, prior to IL-2 therapy, abrogated the enhancing effect of CY on cytolysis while in vivo elimination of T cells by anti-L3T4 and anti-Lyt2 monoclonal antibodies did not, indicating that in the absence of T cell antigenic challenge, the increased cytolytic function after CY administration is probably mediated through NK cells. These findings provide evidence that CY may be used more effectively in IL-2-based immunotherapy protocols, if consideration is given to timing of CY and IL-2 administration.

Original languageEnglish (US)
Pages (from-to)74-78
Number of pages5
JournalCancer Immunology Immunotherapy
Volume34
Issue number2
DOIs
StatePublished - Mar 1 1991
Externally publishedYes

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Keywords

  • Cyclophosphamide
  • Cytolysis
  • IL-2, NK activity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Katsanis, E., Bausero, M. A., Ochoa, A. C., Loeffler, C. M., Blazar, B. R., Leonard, A. S., & Anderson, P. M. (1991). Importance in timing of cyclophosphamide on the enhancement of interleukin-2-induced cytolysis. Cancer Immunology Immunotherapy, 34(2), 74-78. https://doi.org/10.1007/BF01741339