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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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

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Liposomes
Interleukin-2
Neoplasm Metastasis
T-Lymphocytes
Liver
Monoclonal Antibodies
Congenic Mice
Adoptive Immunotherapy
Lymphocyte Activation
Immunotherapy
Colon
Adenocarcinoma
Therapeutics
Cell Count
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Loeffler, C. M., Platt, J. L., Anderson, P. M., Katsanis, E., Ochoa, J. B., Urba, W. J., ... 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.

Antitumor effects of interleukin 2 liposomes and anti-CD3-stimulated T-cells against murine MCA-38 hepatic metastasis. / Loeffler, Cynthia M.; Platt, Jeffrey L.; Anderson, Peter M.; Katsanis, Emmanuel; Ochoa, Juan B.; Urba, Walter J.; Longo, Dan L.; Leonard, Arnold S.; Ochoa, Augusto C.

In: Cancer Research, Vol. 51, No. 8, 15.04.1991, p. 2127-2132.

Research output: Contribution to journalArticle

Loeffler, CM, Platt, JL, Anderson, PM, Katsanis, E, Ochoa, JB, Urba, WJ, Longo, DL, Leonard, AS & Ochoa, AC 1991, 'Antitumor effects of interleukin 2 liposomes and anti-CD3-stimulated T-cells against murine MCA-38 hepatic metastasis', Cancer Research, vol. 51, no. 8, pp. 2127-2132.
Loeffler, Cynthia M. ; Platt, Jeffrey L. ; Anderson, Peter M. ; Katsanis, Emmanuel ; Ochoa, Juan B. ; Urba, Walter J. ; Longo, Dan L. ; Leonard, Arnold S. ; Ochoa, Augusto C. / Antitumor effects of interleukin 2 liposomes and anti-CD3-stimulated T-cells against murine MCA-38 hepatic metastasis. In: Cancer Research. 1991 ; Vol. 51, No. 8. pp. 2127-2132.
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