Protocol Number: 98-C-0139

Title:

Vaccine Therapy with Tumor Specific Mutated VHL Peptides in Adult Cancer Patients with Renal Cell Carcinoma

Number:

98-C-0139

Summary:

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 (VHL) gene which is associated with the development of the VHL disease, has been recently mapped and cloned, and 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, we propose to treat patients with sporadic RCC who carry VHL mutations in their tumors with corresponding mutant VHL peptide vaccination. This vaccination will be done either by using pulsed-autologous peripheral mononuclear cells with the peptides, or peptides administered subcutaneously alone or in combination with cytokines.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Follow-up Of Previously Enrolled Subjects Only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions: Currently Not Provided

Disease Category:

PROTICD

Keywords:

Immunotherapy

Kidney

Genes

Recruitment Keywords:

None

Conditions:

Renal Cell Carcinoma

Investigational Drug(s):

VHL Peptide

Montanide ISA-51

Investigational Device(s):

None

Contacts:

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citations:

Cytokines and cytotoxic agents in renal cell carcinoma: a review

Low dose interleukin-2 treatment of metastatic renal cell carcinoma

High dose interleukin-2 in the therapy of metastatic renal cell carcinoma

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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Warren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/16/2004