Prospects for interleukin-2 therapy in hematologic malignant neoplasms.
Interleukin-2 (IL-2) is a regulator of diverse functions of the immune system that can induce regressions in some experimental and human tumors. These early findings suggest a potential role for IL-2 in the treatment of certain malignant neoplasms including lymphomas and leukemias. Advanced, rapidly growing tumors are generally not amenable to immunotherapy. Therefore, it is more likely that protocols with IL-2 will be used to prolong remission and prevent relapse in leukemia patients with minimal tumor load. Several approaches are currently being tested in animal experiments and clinical trials. Activation of tumor-reactive lymphocytes (specific or nonspecific) by IL-2 in vivo may eradicate residual leukemia in patients with occult disease. In vitro-propagated autologous or allogeneic leukemia-reactive T cells may be infused with IL-2 to facilitate the tumor destruction. The IL-2 enhances monoclonal antibody-dependent effector systems, such as antibody-dependent cell-mediated cytotoxicity in vivo. Monoclonal antibodies recognizing epitopes on leukemia/lymphoma cells could therefore be used with IL-2 to target nonspecific effectors to destroy tumor cells. Other cytokines appear to potentiate various antitumor activities of IL-2, including cytotoxicity of antigen-specific T lymphocytes or lymphokine-activated killer cells in vitro, and these combined effects may be exploited in clinical trials in which more than one cytokine is used simultaneously or in sequence. Finally, a stepwise completion of clinical protocols testing this immunologic approach in combination with other treatment modalities is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)
Malkovska
V
V
Department of Medicine, University of Wisconsin Hospital and Clinics, Madison.
Sondel
P M
PM
D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007938:Leukemia / Q000628:therapy*; D008223:Lymphoma / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000502:physiology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2