T cell recognition and immune editing in SCLC (C05)

• Subject Area: Immunology ; General Genetics and Functional Genome Biology ; Hematology, Oncology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413326622

U. Sahin and L. Kolb together with their team will strive to identify additional T cell receptor (TCR) sequences of tumor-cell-reactive T cells identified by single cell sequencing of primary human SCLC tumors, provided by Z01 and C01. The team will further pursue the discovery of tumor-specific neoantigens by transcriptome sequencing. They will then seek to validate the predictive T cell reactivity by means of cloning of the newly identified TCR and ectopic expression in a cellular model, combined with presentation of the predicted neoantigen. Escape mechanism of resistant clones will be studied in vitro as well as in vivo in humanized mouse models engrafted with SCLC cell lines upon transfer of TCR engineered adoptive T cells. Working with C01 and C03, the work of C05 is geared toward identifying the molecular features underlying immune recognition and the escape thereof in SCLC.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1399: Mechanisms of drug sensitivity and resistance in small cell lung cancer
• Applicant Institution: Universität zu Köln
• Project Heads: Laura Kolb, Ph.D., since 7/2023; Professor Dr. Ugur Sahin