[Adoptive immunotherapy by intra-arterial infusion of ATLAK or Allo-TLAK cells in patients with head and neck cancer].

ABSTRACT

For clinical application of adoptive immunotherapy, it is necessary to prepare a sufficient number of autologous tumor specific effector cells. A large amount of peripheral blood lymphocytes was obtained by leukapheresis using a Heamonetics V50 pheresis system. Autologous tumor- and lymphokine-activated killer (ATLAK) cells were induced by autologous mixed lymphocyte tumor cell culture (autologous MLTC) and further activation with recombinant interleukin-2 (rIL-2). Another problem was the difficulty of obtaining a sufficient number of highly activated effector cells to reach the target tumor tissue. Direct infusion of effector cells into a feeding artery was effective for cell accumulation in the target. ATLAK cells were infused into maxillary artery in 4 patients with maxillary squamous cell carcinoma. The results indicated that the therapy was effective for reduction of the tumor mass. After immunotherapy, surgery was performed and the tissues were histologically examined. Degenerated tumor cells and intensive infiltration by mononuclear cells and macrophages were seen in the surrounding fibrous tissue. However, the quantity of fresh autologous tumor cells available from open biopsy was limited. Allogeneic cultured tumor cell line was used as stimulator of lymphocytes instead of autologous tumor cells. The killing activity of the allogeneic tumor and lymphokine activated killer (Allo-TLAK) cells was significantly induced against the autologous tumor cells. Antitumor effect was observed in 5 out of 9 patients. Side effects were minor, such as slight fever and blood eosinophilia, which may be due to the rIL-2 function. These results indicate that this method of therapy is an effective form of adoptive immunotherapy.