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Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial

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Abstract

 Adoptive immunotherapy (AIT) of cancer with T lymphocytes may be limited by the need to activate tumor antigen-sensitized cells in vitro. In murine models, we have shown that AIT with tumor-sensitized T cells that have been pharmacologically activated with bryostatin 1 and ionomycin plus interleukin-2 can induce tumor regression. A Phase I clinical trial was carried out to assess the feasibility and toxicity associated with using tumor- or vaccine-draining lymph node cells, activated pharmacologically and expanded in culture with low-dose interleukin-2 and infused intravenously, followed by IL-2 infusion. Nine patients were entered into the trial, and six were treated as planned. Average expansion of cell numbers over 13 to 27 days in culture was 118-fold. No patient's cells reached the target cell number (2.5 × 1010). Infusion of these cells did not result in any unexpected toxicities. The toxicities observed were related to IL-2 infusion, and conformed to the expected range of side-effects. Based on these Phase I results, additional trials, with tumor antigen vaccine-sensitized DLN and technical modifications of the culture technique, are planned.

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Received: 18 January 2001 / Accepted: 26 April 2001

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Bear, H., Roberts, J., Cornell, D. et al. Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial. Cancer Immunol Immunother 50, 269–274 (2001). https://doi.org/10.1007/s002620100199

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  • DOI: https://doi.org/10.1007/s002620100199

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