Induction of HLA-A2-restricted CTL responses by a tubular structure carrying human melanoma epitopes.

Mrinal K Ghosh; Cui-Ling Li; Catherine Fayolle; Gilles Dadaglio; Aileen Murphy; François A Lemonnier; Polly Roy ORCID logo; Claude Leclerc; (2002) Induction of HLA-A2-restricted CTL responses by a tubular structure carrying human melanoma epitopes. Vaccine, 20 (19-20). pp. 2463-2473. ISSN 0264-410X DOI: 10.1016/s0264-410x(02)00185-8
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Epitope-based vaccination strategies designed to induce strong tumor-specific CD8(+) T cell responses are being widely considered for cancer immunotherapy. Here, two recombinant tubular structures, NS1-Mela 1 and NS1-Mela 2, carrying, respectively two HLA-A2 epitopes derived from human melanoma antigens were constructed and their capability to induce CTL responses in vivo were studied in HLA-A2 transgenic mice. Strong CTL responses specific for GnT-V/NA 17-A and gp100 (154-162) epitopes were generated in HLA-A2 transgenic mice immunized by the construct NS1-Mela l carrying these two epitopes. The second construct NS1-Mela 2 carrying both Tyrosinase (369-377Da) and Melan-A/Mart-1 (27-35) epitopes induced a weak Tyrosinase-specific CTL response in mice but failed to induce specific CTL responses against the Melan-A/Mart-1 (27-35) epitope in the tested mice. Thus, recombinant tubular structures containing multiple tumoral epitopes may lead to new strategies for the induction of strong tumor-specific CTL responses in cancer patients.

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