Kurzfassung

Important advances in understanding the mechanisms of pathogenesis and in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades. However, despite improved targeted therapy and the use of immune checkpoint blockade inhibitors (ICI), overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new therapies is highly warranted to improve antitumor therapy in NSCLC. The Kirsten rat sarcoma...Important advances in understanding the mechanisms of pathogenesis and in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades. However, despite improved targeted therapy and the use of immune checkpoint blockade inhibitors (ICI), overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new therapies is highly warranted to improve antitumor therapy in NSCLC. The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated proto-oncogenes found in various cancers and dominant single amino acid substitutions at codon 12 such as particularly the G12V mutation occur with high incidence in NSCLC and also in pancreatic adenocarcinoma. Thus, the frequency and tumor specificity of the KRASG12V peptide neoantigen renders this target very attractive for therapeutic purpose. Recent data show infiltrating T cells that evoke antitumor responses to KRAS mutations in patients with NSCLC, but are often hampered by an immunosuppressive tumor microenvironment (TME).
Within an innovative multimodal immunotherapeutic approach we therefore develop a new class of bispecific T cell engagers (BiTEs) composed of a T-cell-receptor (TCR) mimic (TCRm) single chain variable fragment (scFv) of a nanobody recognizing the KRASG12V peptide restricted by the HLA-A*03:01/11:01 superfamily fused to human anti-CD3. This project is carried out in close co-operation with Prof. Dr. M. Peipp (University Hospital Kiel) who has a longstanding experience in developing bispecific antibodies and jointly conducted with PD Dr. E. Bockamp from the Inst. of Translational Immunology.» weiterlesen» einklappen