In C05, U. Sahin will explore neoantigen-specific T cell responses in SCLC cell lines and patient samples to decipher mechanisms of immune recognition and clonal escape. Prediction and identification of mutant neoepitopes presented on HLA class I and II molecules will be performed in clinical specimens. The group will identify tumor reactive neoantigen-specific CD4⁺ and CD8⁺ T cells. Potential TCR pairs will be cloned and reconstituted in reporter T cells to validate functional properties (recognition, cytotoxicity) on SCLC cell lines. The respective TCR sequence information will be linked to predicted neoantigens. The impact of immune selection and potential outgrowth of antigen escape variants will then be evaluated in in vitro co-cultures of neoantigen-specific T cells and SCLC cell lines, as well as in vivo in SCLC mouse models. Finally, the group will perform therapeutic vaccination studies in vivo.