Abstract
6047 Background: Response rates to anti-PD1 antibodies in head and neck squamous cell carcinoma (HNSCC) range from 13-20% in recurrent / metastatic disease and up to 50% in locoregionally advanced disease. Vaccines composed of tumor-exclusive antigens may increase response rates to immunotherapy. We have previously identified HLA-presented tumor-exclusive peptides (TEP) in a cohort of 40 oropharyngeal HNSCC (UL dataset) and defined a warehouse of HLA allotype specific TEP (EP2023/071063, patent pending) for semipersonalized vaccine composition for 15 HLA allotypes. Methods: The HLA-bound immunopeptidome of a validation cohort of 40 HNSCC from Tübingen University was analyzed by tandem mass spectrometry (TÜ dataset). Data were processed as previously described to identify TEP. The TÜ dataset was queried for TEP from the previously defined warehouse containing 48 TEP for the respective 15 HLA allotypes in a cohort of 40 oropharyngeal HNSCC (UL dataset) patient samles. Coverage was defined as the fraction of patients presenting at least one of the TEP for a certain HLA allotype. Results: Among all 80 patients, 75 had at least one of the 15 HLA allotypes (36 in the TÜ cohort and 39 in the UL cohort). Of the 48 TEP, 28 TEP for 11/15 HLA allotypes were found in the TÜ validation cohort. The best coverages with the warehouse TEP were found for the following four HLA allotypes: HLA-A*01:01 (TÜ: 91%; UL: 79%), A*02:01 (TÜ: 81%; UL: 52%), B*40:01 (TÜ: 63%; UL: 100%) and A*24:02 (TÜ: 60%; 44%.). Based on a semipersonalized TEP selection by HLA allotype, 27/40 patients in the TÜ cohort presented at least one of the TEP selected (range: 0-10), whereas 28/40 patients in the UL cohort presented at least one of the TEP (range: 0-7). Thus, the total cohort coverage based on a semipersonalized peptide selection was 55/80 patients (68.8%). Conclusions: We validated previously identified TEP from oropharyngeal HNSCC for frequently occurring HLA allotypes in an independent, equally sized cohort of HNSCC patients. A semipersonalized vaccine composition strategy using a warehouse / off-the-shelve approach for immunotherapy trials seems feasible.
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