Interleukin-2 antitumor and effector cell responses.
Based on the above considerations, there are a number of implications for the clinical development of rIL-2 that depend on the putative effector cell. If the effector cell responsible for rIL-2-mediated antitumor effects is the LAK cell, effective treatment regimens will likely continue to require extremely high doses of rIL-2. Based on preclinical models, one would also predict that LAK cell-mediated tumor killing against nonimmunogenic tumors would be most effective in low tumor burden states and could only be demonstrated clinically in large-scale, randomized, adjuvant trials. On the other hand, some weakly immunogenic tumors might be susceptible to CTL-mediated killing even when disease was further advanced. The antitumor activity of rIL-2 in patients with large tumors suggests that this might be the case for some patients with RCC. Treatment approaches that result in the generation of relevant effector cell populations would be expected to markedly enhance CTL-dependent rIL-2 antitumor activity. However, unless antigenic heterogeneity was minimal, multiple tumor antigen-specific T-cell populations would have to be generated for responses to be complete and durable.
Hawkins
M J
MJ
Lombardi Cancer Research Center, Washington, DC 20007.
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000628:therapy; D002986:Clinical Trials as Topic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000502:physiology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D016219:Immunotherapy, Adoptive; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000628:therapy; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins