It was found to induce a pronounced intratumoral infiltrate of macrophages, CD4 + and CD8 + T cells, and a cytokine profile similar to Th1 immune response ( 20). ADV/HSV-tk gene transduction followed by acyclovir prodrug ganciclovir or valacyclovir therapy has shown both local and systemic antitumor activity in several cancer models ( 17–19). Adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) can catalyze the phosphorylation of acyclovir to a toxic form capable of inhibiting DNA synthesis and resulting in selective cytotoxicity to cells expressing HSV-tk ( 16). Different strategies have been applied to enhance abscopal effect. IntroductionĮven though abscopal effect has been reported, the overall occurrence rate is low ( 15). We believe these findings will be of interest to the readers in the era of immunotherapy. Our correlative immune profile analysis using Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) on paired blood samples and biopsies suggested increase of CD8 T cells and myeloid cells as predictive markers of response and non-response, respectively. Patients with clinical benefit had durable responses. We observed an enhanced clinical benefit rate using this combination strategy in a previously heavily treated population, including patients with low/negative PD-L1 tumors and patients with liver metastases. Patients were treated with the combination of in situ adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy, followed by radiation and then pembrolizumab (STOMP). In this Phase 2 trial in metastatic triple-negative breast cancer (TNBC) patients, evaluated the efficacy and safety of combining two additional modalities to enhance efficacy of immune checkpoint blockade.
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