) Although standard chemotherapy induces a remission in 70-90% of adult patients with acute lymphocytic leukemia (ALL), over half of such patients ultimately relapse, most likely due to the presence of drug-resistant leukemia cells. Therefore, the primary goal of this proposal is to develop strategies for the generation of an autologous antitumor immune response that overcomes the phenomenon of drug resistance in patients in ALL, thereby increasing the likelihood that patients in remission may be cured. Two strategies are envisioned: (1) induction of an autoinunune syndrome with antitumor efficacy by Cyclosporine A (CsA) treatment following standard consolidation chemotherapy, and (2) active specific immunization with killed autologous tumor cells obtained from the patients at diagnosis.
The specific aims of the proposal are to: 1) Detemine if autoimmunity can be induced by treating ALL patients with CsA following consolidation chemotherapy. 2) Optimize conditions for generating cytotoxic T lymphocyte responses to autologous tumor vaccines by: a) characterizing the regeneration of T lymphocyte and antigen presenting cells after consolidation chemotherapy, b) assessing the effects of CsA on self-tolerance induction and GM-CSF on immune ontogeny following consolidation chemotherapy; and c) verifying the integrity of the reconstituted immune system by measuring the immune response to recall antigens as well as the recombinant hepatitis B vaccine at varied intervals following consolidation chemotherapy. 3) Undertake pilot trials of leukemia cell acquisition, purification, and storage for later use as specific tumor vaccines.
