Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 2589
© 2004 American Society of Clinical Oncology

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Abstract

Vaccine therapy with tumor specific mutated VHL peptides in adult cancer patients with renal cell carcinoma

NCI, Bethesda, MD

2589

Background: Chemotherapy in metastatic renal cell carcinoma is ineffective. Although Interferon and IL-2 have been used with some success, there is a long way to go to achieve satisfactory results. Despite the success of local treatment in early disease, the overall survival is around 50%. Therefore, the development of another therapeutic approach is needed. Human cancers are commonly associated with mutations in oncogenes. These mutated genes produce proteins that are unique to cancer cells. The von Hipple-Lindau (VHL) gene was found to be mutated in 57% of sporadic renal cell carcinomas. 40 - 90% of these mutations are frame shift, 90% of the rest of the mutations are mis-sense point mutations, and very few are nonsense or stop mutations. Novel mutant proteins are processed and displayed as short peptides through HLA molecules on the tumor cell surface. Thus, mutant VHL protein can be an attractive vaccine therapy target. Methods: : In previous clinical trials, vaccination with peptide spanning the patient's mutations in Ras and P53 produced specific immunological responses. Specific lymphocytes, whetherCD4+ or CD8+, were generated that specifically recognized the mutant peptide with which the patient was vaccinated. On this trial, we treated 5 patients with advanced renal carcinoma with 1000 µg of the corresponding mutant VHL peptide mixed with Montanide ISA-51 adjuvant subcutaneously (SQ). Vaccine cycles were repeated every 4 weeks for a total of four vaccinations. Results: No grade 3 or grade 4 toxicities occurred. Grade I-II toxicities resolved spontaneously. Three of five patients showed evidence of lack of progression after four vaccinations (2 ms, 4 ms, 5.5 ms, 8.5ms+, 25ms+) and continued to receive additional vaccinations. Two patients started the vaccinations NED (no evidence of disease) and remained NED. For the first time, specific immunological responses for the mutant VHL peptides have been demonstrated by Elispot assay. Conclusions: We believe that this treatment may form a potentially promising approach in combination with other therapeutic modalities in metastatic renal cell carcinoma.

No significant financial relationships to disclose.

Abstract presentation from the 2004 ASCO Annual Meeting