Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma
About 27,000 new cases of renal cell carcinoma (RCC) are diagnosed every year in the United
States. 11,000 of these cases will die from the disease. More than half of patients
present with advanced or metastatic disease for which chemotherapy plays a very limited
role. Therefore, development of another therapeutic approach is needed. Cancers in humans
are commonly associated with mutations in dominant and recessive oncogenes. These genes
produce mutated proteins that are unique to cancer cells. Von Hipple-Lindau gene, which is
associated with the development of the VHL disease, has been recently mapped and cloned; it
is found to be mutated in 57% of sporadic renal cell carcinomas.
Data in mice have shown the generation of MHC restricted CTL that are capable of detecting
endogenous cytoplasmic peptide derived from mutated oncogenes. In addition, we have
recently demonstrated, by conducting different phase I clinical trials in which we vaccinate
cancer patients with mutated Ras or p53 peptides corresponding to the abnormality patients
harbor in their tumors, that in some patients we can generate immunological responses
represented by the generation of lymphocytes (CD4+ and/or CD8+). In the current study, we
would like to extend our observations to test whether VHL tumor suppressor protein can be
immunologically targeted by vaccination. We have identified specific epitopes along the
amino acid sequence of the VHL protein which represent known specific HLA class-I binding
motifs. These amino acids stretches in the VHL protein correspond to the area of the point
mutation hot spots. Therefore, this protocol treats patients with sporadic RCC who carry
VHL mutations in their tumors with corresponding mutant VHL peptide vaccination.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Percentage of Participants Who Generated an Immune Response
The immunological response was assessed by in-vitro T cell cytokine production enzyme-linked immunosorbent spot (ELISPOT). From each patients, post-vaccination peripheral blood mononuclear cells (PBMC) were compared to pre-vaccination as a baseline. A positive ELISPOT result for the patients was defined as a total number of experimental spots in the post-vaccination sample of more than twofold above the total spots in the pre-vaccination sample.
Samir N Khleif, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
|National Cancer Institute, National Institutes of Health||Bethesda, Maryland 20892|