Adoptive immunotherapy mediated by anti-TCR/IL-2-activated tumour-draining lymph node cells

The adoptive immunotherapy of cancer with sensitized T lymphocytes is well documented in several animal models. These studies indicate the existence of precursor lymphocytes, in the tumour-bearing animals, which can acquire therapeutic efficacy after in vitro manipulations. To generate immune effector cells, these precursor lymphocytes have to be antigenically stimulated in vitro by the tumour of origin. Using the weakly immunogenic MCA 205 and MCA 203 murine sarcomas, we demonstrate here that this in vitro antigenic stimulation can be achieved by sequential activation with anti-T-cell receptor (TCR) monoclonal antibody and interleukin-2 (IL-2). The culture of tumour-draining lymph node (TDLN) cells with anti-TCR/IL-2 resulted in an up to eightfold increase in cell numbers. The adoptive transfer of these activated cells mediated a significant reduction of 3-day established pulmonary metastases. Although this antibody could activate all of the TCR alpha beta-bearing T cells non-specifically, the therapeutic efficacy mediated by anti-TCR/IL-2-activated cells was tumour specific. Treatment of MCA 205 advanced pulmonary metastases resulted in prolongation of survival, and 30% of treated mice were tumour free for more than 90 days. These tumour-free mice rejected a challenge of MCA 205 but not MCA 203, indicating the development of long-lasting systemic tumour immunity. In spite of their in vivo anti-tumour efficacy, the anti-TCR/IL-2-activated TDLN cells did not exhibit detectable in vitro cytotoxicity. These results demonstrate that this activation method could be an alternative way to generating potent anti-tumour effector T cells.