ZIA BC 010756 (ZIA) | |||
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Title | Development a combined prophylactic and therapeutic cervical cancer vaccine u | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Khleif, Samir | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $52,766 | Project Dates | 10/01/2005 - N/A |
Fiscal Year | 2010 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Digestive Diseases (5.0%) |
Anus (5.0%) Cervical Cancer (80.0%) Penis (5.0%) Vaginal (5.0%) |
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Research Type | |||
Vaccines Systemic Therapies - Clinical Applications |
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Abstract | |||
The HPV16 E2 protein is uniformly expressed during productive viral infection. It has been reported that T cell responses to E2 are inversely correlated with risk of cervical cancer. E2 is an important target for immune-mediated clearance of HPV mediated cervical lesions. Our previous study demonstrated that immune response to HPV E2 could be induced by multiple immunizations with the combined chimeric virus-like particles and E2 peptides (J. Int. Cancer 2006). As CD8+ T cell response to E2 can be induced only with multiple immunizations. To enhance the immunogenicity of E2, we modified the E2 epitope 138-147 by substituting positions 139 and 140 from isoleucine-cysteine to leucine-alanine (E2-138-147LA). This modified peptide demonstrated a higher affinity for HLA-A2 in a T2 binding assay than the wild type one and induced a CD8+ T cell response by a signal peptide immunization (with GM-CSF and anti-CD40) in HLA-A2 transgenic mice. We have established a tumor cell line expressing a E2 protein. Spleen cells from mice immunized either with wild type or modified E2 peptide can lyse tumor cell line expressing E2. Thus, the E2 peptides? based vaccine has a potential to be considered as vaccine targeting early HPV16-imediated neoplastic lesions (NCI patent: E-155-2005 and a manuscript in preparation). |