Antitumor effects of interleukin-7 and adoptive immunotherapy on human colon carcinoma xenografts

William J Murphy, Timothy C. Back, Kevin C. Conlon, Kristin L. Komschlies, John R. Ortaldo, Thomas J. Sayers, Robert H. Wiltrout, Dan L. Longo

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The antitumor properties of recombinant human IL-7 (rhIL-7) on a human tumor was evaluated by engrafting a human colon carcinoma into immunodeficient mice and then treating the mice with rhIL-7 and adoptively transferred human peripheral blood T cells. It was found that rhIL-7 alone had no effect on the survival of the tumor-bearing recipients. However, the combination of rhIL-7 and human T cells significantly promoted the survival of the recipients compared with mice receiving either treatment by itself. When the surviving mice were analyzed 6 mo later for the degree of human cell engraftment, the recipients receiving both rhIL-7 and human T cells had greater numbers of human CD8+ T cells in the spleens. However, the human T cells recovered from the surviving mice showed low lytic activity against the tumor in vitro. Supernatants from human T cells cultured with the tumor and rhIL-7 in vitro were found to inhibit tumor growth and were demonstrated to contain high levels of IFN-γ. Antibodies to IFN-γ neutralized the growth inhibition of the tumor both in vitro and in vivo demonstrating that the in vivo mechanism underlying the antitumor effects of this regimen was partly dependent on the production of IFN-γ by the T cells and not their cytolytic capability. Interestingly, systemic administration of rhIFN-γ to tumor-bearing mice yielded little antitumor effect suggesting that adoptive immunotherapy with rhIL-7 was superior possibly because of the continuous local release of the cytokines. Therefore, rhIL-7 may be of clinical use as an antineoplastic agent and the human/mouse model is a potentially important preclinical model for in vivo evaluation of the efficacy of this and other immuno-therapies.

Original languageEnglish (US)
Pages (from-to)1918-1924
Number of pages7
JournalJournal of Clinical Investigation
Volume92
Issue number4
StatePublished - 1993
Externally publishedYes

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Adoptive Immunotherapy
Interleukin-7
Heterografts
Colon
Carcinoma
T-Lymphocytes
Neoplasms

Keywords

  • Cancer treatment
  • Cytokines
  • Interleukin-7
  • SCID/human mouse
  • T cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Murphy, W. J., Back, T. C., Conlon, K. C., Komschlies, K. L., Ortaldo, J. R., Sayers, T. J., ... Longo, D. L. (1993). Antitumor effects of interleukin-7 and adoptive immunotherapy on human colon carcinoma xenografts. Journal of Clinical Investigation, 92(4), 1918-1924.

Antitumor effects of interleukin-7 and adoptive immunotherapy on human colon carcinoma xenografts. / Murphy, William J; Back, Timothy C.; Conlon, Kevin C.; Komschlies, Kristin L.; Ortaldo, John R.; Sayers, Thomas J.; Wiltrout, Robert H.; Longo, Dan L.

In: Journal of Clinical Investigation, Vol. 92, No. 4, 1993, p. 1918-1924.

Research output: Contribution to journalArticle

Murphy, WJ, Back, TC, Conlon, KC, Komschlies, KL, Ortaldo, JR, Sayers, TJ, Wiltrout, RH & Longo, DL 1993, 'Antitumor effects of interleukin-7 and adoptive immunotherapy on human colon carcinoma xenografts', Journal of Clinical Investigation, vol. 92, no. 4, pp. 1918-1924.
Murphy, William J ; Back, Timothy C. ; Conlon, Kevin C. ; Komschlies, Kristin L. ; Ortaldo, John R. ; Sayers, Thomas J. ; Wiltrout, Robert H. ; Longo, Dan L. / Antitumor effects of interleukin-7 and adoptive immunotherapy on human colon carcinoma xenografts. In: Journal of Clinical Investigation. 1993 ; Vol. 92, No. 4. pp. 1918-1924.
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