Antitumor Effects of Interleukin 2 Liposomes and Anti-CD3-Stimulated T-Cells against Murine MCA-38 Hepatic Metastasis

Cynthia M. Loeffler, Jeffrey L. Platt, Peter M. Anderson, Emmanuel Katsanis, Juan B. Ochoa, Walter J. Urba, Dan L. Longo, Arnold S. Leonard, Augusto C. Ochoa

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49 Scopus citations

Abstract

The stimulation of murine splenocytes with the monoclonal antibody anti-CD3 and interleukin 2 (IL-2) results in the propagation of large numbers of cells (T-activated killer; T-AK) which demonstrate high therapeutic efficacy when infused with IL-2 into mice bearing pulmonary metastases. Interleukin 2 infusions are required to maintain the function of the adoptively transferred cells. Recent data demonstrate that the therapeutic efficacy can be enhanced by encapsulating IL-2 in liposomes. The present work tested the combination of T-AK cells with IL-2 liposomes in an immunotherapy model utilizing the MCA-38 murine colon adenocarcinoma. Expansion of murine splenocytes was achieved with anti-CD3 monoclonal antibody plus IL-2 and was consistently greater than 50-fold during a 9-day culture period. Cytolytic activity of the murine T-AK cells was mediated primarily by Lyt-2+ cells. In vivo results demonstrate synergistic therapeutic efficacy of the combination of IL-2 liposomes and T-AK cells. Evaluation of the in vivo distribution of these T-AK cells utilizing congenic mice demonstrates that Lyt-2+ cells from these in vitro cultures infiltrate hepatic metastases in vivo. The activation of lymphocytes with anti-CD3 monoclonal antibody and IL-2 appears to be a reproducible and convenient method of producing cells capable of producing antitumor effects in models of adoptive immunotherapy.

Original languageEnglish (US)
Pages (from-to)2127-2132
Number of pages6
JournalCancer Research
Volume51
Issue number8
StatePublished - Apr 15 1991
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Loeffler, C. M., Platt, J. L., Anderson, P. M., Katsanis, E., Ochoa, J. B., Urba, W. J., Longo, D. L., Leonard, A. S., & Ochoa, A. C. (1991). Antitumor Effects of Interleukin 2 Liposomes and Anti-CD3-Stimulated T-Cells against Murine MCA-38 Hepatic Metastasis. Cancer Research, 51(8), 2127-2132.