Immunotherapy for renal cell carcinoma.
Renal cell carcinoma (RCC) is the most prevalent malignancy within the kidney and the incidence is rising. Due to improved radiological evaluation over 50% of the renal cancers are found incidentally. Despite the fact that these incidentalomas are often confined to the kidney, around 50% of all patients diagnosed with kidney cancer will develop systemic disease. Metastatic RCC has a poor prognosis. Traditional treatment modalities like chemo- and radiotherapy show overall response percentages of 2-6%. In view of the observed spontaneous remissions of advanced renal cancer, immune mechanisms have been suggested to play a role in the natural disease course of RCC. At present, several non-specific cytokine regimens are used in the treatment of mRCC, e.g. interleukin-2 and interferon-alpha, in combination or as monotherapy or in combination with substances like 13-cis-retinoic acid and/or 5-fluorouracil. Collective data of trials evaluating cytokine-based therapies for mRCC show an overall response rate of approximately 15%, with 5% of the patients showing complete responses. More importantly, cytokine treatment clearly translates into a significant survival benefit in a subset of patients. Nevertheless, the toxicity profile of these cytokine regimens is significant. With the enhanced knowledge of tumor-immunology, the identification of immunogenic tumor proteins, and antibodies recognizing tumor-associated antigens, new treatment strategies with increased specificity and fewer side effects are of interest. Here we review the different immunotherapeutical modalities currently used as well as new approaches for the treatment of advanced RCC.
Bleumer
Ivar
I
Department of Urology, University Medical Center, St Radboud, Geert Grooteplein 10, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Oosterwijk
Egbert
E
De Mulder
Pieter
P
Mulders
Peter F A
PF
D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016233:Immunotherapy, Active / Q000379:methods; D007372:Interferons / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D007376:Interleukin-2; D007372:Interferons