P01.01 Autologous live cell vaccination prolongs survival in immunotherapy-resistant glioma models

frequently expressed in SCLC (small cell lung cancer).Initial pMHC binder candidate designs were generated using RFdiffusion, 2 followed by a custom-made iterative refinement algorithm.To experimentally identify specific binders, we implemented a high-throughput library screening strategy utilising mammalian cell surface expression.Positive cells were sorted via HLA-A*02-IGFBPL-1 tetramer staining, with enriched binders identified via next-generation sequencing.These screening hits were incorporated as binding moieties of peptide-centric CARs for functional validation in primary human T cells. ResultsWe achieved an initial binder design success rate of <1%, improving to 2.9% post iterative refinement.Top binder candidates were successfully integrated and transduced into primary human T cells.IGFBPL-1 peptide-centric CARs demonstrated significant functional activity upon co-culture with IGF-BPL-1 peptide-pulsed HLA class I-matched target cells, assessed through target killing, cytokine release and expansion.We further demonstrated target specific activation of our IGBFPL-1 peptide-centric CARs against endogenous expression of IGFB-PL-1 peptide on multiple HLA-A*02 SCLC cell lines.Ongoing efforts aim to further characterize IGFBPL-1 peptide centric CAR functionality in vitro and in vivo, with optomisation continuing in both the refinement of the IGFBPL-1 binders and CAR receptor construct pairing.Conclusion This work presents a significant advance in targeting previously inaccessible intracellular oncoproteins with CAR T cells in SCLC.It also exemplifies the comparative speed and cost-effectiveness of the rational design of peptide centric binders, expanding the diversity of targets accessible to researchers.