INDUCTION OF ANTITUMOR LYMPHOCYTES IN CANCER-PATIENTS AFTER BRIEF EXPOSURE TO SUPERNATANTS FROM CULTURES OF ANTI-CD3-STIMULATED ALLOGENEIC LYMPHOCYTES

The present study investigated the ability of supernatants collected f rom cultures of healthy donor-derived peripheral blood mononuclear cel ls (HD-PBMCs) stimulated with anti-CDS monoclonal antibody (MAb) (allo geneic CD3 supernatants; ACD3S) to induce, upon brief exposure, tumour -reactive cytotoxic lymphocytes in cancer patients' PBMCs. ACD3S enhan ced natural killer (NK) and lymphokine-activated killer (LAK) cell-med iated cytotoxicity ACD3S contained increased levels of interleukins (I L) 1, 2, 6, 7 and 12, as well as of granulocyte-macrophage colony-stim ulating factor (GM-CSF), gamma-interferon (IFN-gamma) and tumour necro sis factor-alpha (TNF-alpha). MAbs against these cytokines significant ly reduced the ACD3S-induced cytotoxicity. ACD3S-induced cytotoxicity was not inhibited by anti-CD4, CD8 and MHC class I MAbs, but was marke dly reduced in the presence of MAb against CD18. In contrast to HD-PBM C, ACD3S derived from cancer patients' lymphocytes exhibited lower lev els of the above-mentioned cytokines and exerted reduced biological ac tivity. In conclusion, ACD3S are able to activate, upon short-term inc ubation, tumour-reactive lymphocytes from cancer patients' PBMCs that lyse a variety of tumour targets, including autologous rumours. ACD3S contain high levels of certain cytokines that positively influence the induction of autologous tumour-reactive lymphocytes. Such supernatant s can be collected easily from healthy donors and stored until use in clinical trials for adoptive cellular therapy of cancer. They may also be indicated in the construction of cytokine cocktails that have the ability to induce antitumour cytotoxicity.