Autologous activated lymphocyte therapy in a community hospital

In the authors' institution patients suffering from metastatic melanoma, renal cell carcinoma or mesothelioma, resistant to conventional therapeutic modilities, are treated with adoptive immunotherapy. Tumour infiltrating lymphocytes (TIL) are prepared from surgical samples and expanded ex vivo in the presence of recombinant interleukin-2 (rIL-2). When sufficient amount of cells are available (5 x 10(9)-10(10)) they are being reinfused. The patients also receive rIL-2 subcutaneously to support the activity and proliferation of reinfused TIL, and to avoid side effects caused by bolus or continuous intravenous administration. Leukapheresed lymphocytes activated by conditioned medium from OKT3 stimulated autologous lymphocytes and rIL-2 (autologous activated lymphocytes, AAL) are used as an alternative when TIL is not available or until it can be produced in sufficient amount. Subcutaneous IL-2 and oral cimetidine are also administered to support the reinfused AAL and to inhibit activation of CD8+ suppressor cells, respectively. Expression of activation markers CD25 and HLA-DR are monitored by flow cytometry as well as cytotoxicity is measured against K562 (NK specific target), HeLa (AALT specific) and against allogeneic or autologous tumour cell targets with a non-radioactive test. Methods are discussed by which the therapeutic efficiency of infused lymphocyte preparations can be improved.