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

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.