Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy
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Genomic profiles relating to H101 treatment-induced alterations are yet to be achieved. Here, we evaluated the impact of H101 via exome-sequencing approaches aiming to probe for potential biomarkers that are actionable in the treatment of persistent/recurrent/metastatic (P/R/M) cervical cancer. Whole exome sequencing (WES) was performd on paired pre- and post-H101 samples from 17 P/R/M cervical cancer patients who received serial intra-tumor injections of H101. Somatic mutations, including high-frequency mutations, microsatellite instability (MSI) status, tumor mutation burden (TMB), clonal evolution, and mutational signature were analyzed. The median follow-up time after the H101 treatment was 14 months. Complete response was achieved in 9 patients, 3 patients achieved partial response, and 2 patients had stable disease, resulting in an objective response rate (ORR) of 70.6% (95% CI: 46.4%-96.7%). WES analysis showed no difference in treatment-related mutation characteristics, including non-synonymous-SNVs and TMB status. Patients with lower TMB were correlated with improved H101 response rates ( We conducted an unprecedented work via a WES-based approach and provided preliminary insights into H101 treatment-induced genetic aberrations in which some genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) could be considered potential therapeutic targets of H101-containing treatment in cervical carcinoma. Moreover, the therapy-associated characteristics such as clonal evolution and a mutational signature may warrant further evaluation of H101 in clinical settings for treating cervical carcinoma.