On October 24, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported the publication of a study in the peer-reviewed journal, Nature Gene Therapy (an open access article; View Source), demonstrating that the newly optimized intratumoral IL-12 immunotherapy platform (electroporation-mediated intratumoral IL-12 gene therapy) induces immunological changes in both locally-treated and distant, untreated tumors (Press release, OncoSec Medical, OCT 24, 2018, View Source [SID1234530143]). The publication provides new mechanistic insights into this systemic anti-tumor immunity including the observation that IL-12 primed effector T cells diminished expression of PD-1, which is particularly relevant to Oncosec’s ongoing KEYNOTE-695 clinical study.
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The paper, titled "Characterization of abscopal effects of intratumoral electroporation-mediated IL-12 gene therapy," by Mukhopadhyay et al., reported results from a pre-clinical study of OncoSec’s optimized plasmid IL-12 (TAVO) therapeutic platform on both locally-treated and distant, untreated lesions, with a particular emphasis on understanding "abscopal" effects in distant non-electroporated tumors. Results from the study indicated that intratumoral IL-12 treatment led to an induction of IL-12-regulated genes, other cytokines and chemokines pathways, as well as genes for enhanced antigen processing and presentation in the treated tumor. These localized IL-12-mediated effects then led to the generation of systemic anti-tumor immune responses, including a surge of CD8+ T cells in the spleen and in non-treated tumors and when coupled with PD-1 modulation, suggests an orchestrated "armoring" of these effector T cells against T-cell checkpoints when primed in the presence of IL-12 in situ.
"Data from previously completed clinical and pre-clinical studies of our TAVO platform in multiple cancer settings has clearly demonstrated that our intratumoral electroporation-mediated IL-12 gene therapy is safe and produces systemic anti-tumor effects from a local delivery of this potent cytokine," said Christopher G. Twitty, PhD, Chief Scientific Officer of OncoSec. "Based on these outcomes, OncoSec is advancing an optimized version of TAVO that is designed to increase transgene expression and efficacy. The study published in Gene Therapy indicates that tumors treated directly with the optimized TAVO therapy rapidly engage IL-12/IFN-g regulated pathways, altering the tumor microenvironment’s immunogenicity and effectively creating an in situ vaccine that ultimately drives an increase of tumor infiltrating lymphocytes and immune-specific gene expression in both treated and distant untreated tumors, indicative of a de novo immune response. These results confirm that OncoSec’s TAVO platform may represent a mechanism by which local intratumoral IL-12 gene therapy can deliver a safe and effective abscopal response."