LAUSR

Adoptive cellular therapy (ACT) has dramatically changed the landscape of cancer immunotherapy. ACTolog® and ACTengine® are actively personalized ACT approaches employing T-cell receptor products based on a warehouse of human leucocyte antigen (HLA)-bound peptide targets. Selecting the relevant target candidates requires the establishment of biomarkers predictive for HLA peptide presentation and their development into companion diagnostic devices. Here we describe the development of IMA_Detect, a diagnostic test based on gene expression analysis of primary patient tumor material by qPCR which is predictive for presentation of a target peptide by HLA. To establish mRNA expression levels which indicate actual peptide presentation, data of Immatics9 XPRESIDENT® target discovery platform was used by integrating quantitative immunopeptidomics data (label-free LC-MS) with paired transcriptomics data (RNA-Seq). The peptide-specific correlation between peptide presentation and expression of the coding exons was verified for each target individually. The resulting RNA-Seq thresholds were mapped to qPCR thresholds using calibration curves followed by validation of the qPCR assay. The IMA_Detect test is performed in a CLIA/CAP approved setting and is currently being applied in the phase I ACT trials IMA101-101 and IMA201-101 to determine whether a patient9s tumor expresses any of the tested targets at levels considered sufficient for potential benefit from the administered T-cell therapy. IMA101-101 uses autologous T-cell products (ACTolog®) for patients with solid cancers while IMA201-101 is based on TCR-engineered T Cells (ACTengine®) in NSCLC and HNSCC patients. We will present first results of the patient screening and the personalized target selection. Citation Format: Jens Fritsche, Arun Satelli, Helen Horzer, Barbara Rakitsch, Franziska Hoffgaard, Norbert Hilf, Oliver Schoor, Harpreet Singh-Jasuja, Weinschenk Toni. IMA_Detect: Mass spectrometry guided development and clinical application of a companion diagnostic for adoptive cellular therapy against tumor associated HLA peptides [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 662.