Immunotherapy of renal cell carcinoma.
Metastatic renal cell carcinoma remains a frustrating disease to treat. Although there is significant evidence that this tumor is responsive to alterations in the immune system, a complete understanding of the antitumor immune response is still elusive. The early trials have been aimed primarily at nonspecific methods for stimulation of the immune system, with the equal possibility that aside from stimulation of the effector cells responsible for tumor containment, there may be stimulation of other mechanisms that will inhibit this response. The better responses in some cases appear to be in the treatments that produce the most toxicities, though even these treatments only have a 20% to 30% response in most trials. Although the prior trials of immunotherapy have yielded modest results, they have provided a better understanding of the immune system in the oncologic setting. Newer trials are now being directed at combinations of lymphokines, which is the beginning of the application of basic science in the clinical setting. With a better appreciation of the basic science behind the immune response, the current factors available will be put into better therapeutic perspective, and newer factors, including various growth factors, may play an important role in future therapy. Also, the addition of antisuppressor regimens to stimulation trials is a sign of recognition of the complexity of the immune response. Aside from suppressor cells, investigators are beginning to realize that there are circulating proteins probably generated either by the tumor or in response to the tumor that are immunosuppressive (eg, circulating IL-2 receptors). Inhibition of these proteins by pheresis or other methods may provide increased immunoreactivity to the tumors, as has already been shown in a small series. Monoclonal antibodies offer the promise of the most specificity; however, the technology is still far from making this therapy imminently available. Only through additional laboratory and clinical investigation, will significant advances be made.
Graham
S D
SD
Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000628:therapy*
D000276:Adjuvants, Immunologic