Gene immunotherapy of cancer: overview and perspectives

new biological cancer treatments are based on specific immunotherapy includ ing cell and gene therapies. Although attempts are made to develop adoptive immunotherapy of cancer, through for example the genetic modification of t umor infiltrating lymphocytes, the major hopes are located in the active im munotherapy of cancer, also designated <<vaccine>> strategies. More than 1 800 patients have been included in 228 clinical trials based on gene therap y of cancer, with more than half based on immune strategies. The major targ et of these immunotherapeutic trials are patients with melanoma, and viral vectors have been used in more than 50 % of them. The therapeutic strategie s are based on the transfer of genes such as those coding for cytokines (ma inly interleukin-2), HLA allo-molecules, costimulatory molecules, or antige ns, used either alone or in combination. These transfers have been performe d ex vivo, mostly in autologous or allogenic tumor cells, but also in fibro blasts or lymphocytes, and also in vivo, by direct injection of the vectors intratumoraly or subcutaneously. Other strategies are developed, as, for e xample, the successful transfer of the herpes simplex virus thymidine kinas e gene in allogenic lymphocytes to control graft-versus-host disease (GVHD) after injection of these cells for immunotherapy of patients with leukemia , in order to induce a graft versus leukemia reaction (GVL). Some clinical and biological responses have been reported. These first results are very e ncouraging for a field which is only in its infancy. Never molecular basic and clinical researches have been so close. Major efforts have to be spent not only on basic research, but also in clinical research, with the develop ment of high quality clinical trials that because they have their own requi rements, should not be designed as chemotherapeutic trials.