Breast Cancer

Biography

Biography: Stefan B Eichmüller

Abstract

Adoptive transfer of autologous tumor antigen-specific T cells provides an innovative strategy for cancer immunotherapy. The differentiation antigen NY-BR-1 is over-expressed in approx. 60% of all invasive mammary carcinomas, thus representing a potential target for T cell based immunotherapy. As efficient immune attack of tumors depends on the activity of tumor antigen-specific CD4+ effector T cells, NY-BR-1 was screened for the presence of HLA-restricted CD4+ T cell epitopes that could be included in immunological treatment approaches. Splenocytes from HLA-transgenic (HLAtg) mice immunized with recombinant adenovirus (Ad.NY-BR-1) were screened ex vivo for specific activity against a NY-BR-1-derived peptide library. In silico predicted candidate epitopes present among recognized library peptides were used to establish murine CD4+ T cell lines whose HLA-restriction was determined in vitro on peptide loaded T2/DR3 and T2/DR4 target cells. Natural processing of these epitopes by human cells was proven upon specific recognition of human dendritic cells loaded with cell lysates from Ad5. NY-BR-1 infected melanoma cells through the established murine HLA-restricted CD4+ T cell lines. Importantly, reactive CD4+ T cells specific for the identified NY-BR-1-derived epitopes were detected among PBMC of HLA-matched breast cancer patients after long term in vitrorestimulation with synthetic 15mers by intracellular cytokine staining. Moreover, deep sequencing performed on the murine HLA-restricted CD4+ T cell lines established with the new epitopes identified two NY-BR-1-specific TCRs that could potentially serve tools for the generation of autologous TCR-transduced T cells lines for future NY-BR-1-specific adoptive immunotherapy approaches against breast cancer.