Kineta, a biotechnology company focused on the translational development of novel therapies in immuno-oncology, has announced the discovery and characterization of several "hit to lead" small molecule compounds that activate interferon response factor 3 (IRF3) via RIG-I like receptor (RLR) pathways and demonstrate immune-mediated tumor regression in a murine colon carcinoma mouse model.

Furthermore, mice in the study who demonstrated complete tumor regression to initial drug treatment were resistant to tumor re-challenge confirming an adaptive immune response in these animals. The findings were presented on March 22nd at the Keystone Symposia on Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology conference.

"Tumors exist in an immuno-suppressive environment and have many strategies of immune evasion. Kineta’s RLR agonists redirect the immune system to break tumor tolerance and elicit novel antigen-specific T-cell responses", said Shawn Iadonato, chief executive officer of Kineta. "These data are groundbreaking in cancer immuno-therapy as we successfully established tumor immunity in mice that had complete regression to an initial tumor."

In this study, Kineta’s novel small molecule compounds demonstrated two immunomodulatory activities. First, they stimulate the RLR/IRF3 pathway in myeloid cells to induce the secretion of inflammatory chemokines/cytokines by human peripheral blood mononuclear cells and dendritic cells. Second, they induce immunogenic cell death in the CT26 colon carcinoma model. Inducing ICD in tumor cells results in the release of danger signals including ATP, HMGB1, and calreticulin that ultimately enhance immune recognition of the tumor.

"When ICD is elicited in tumor cells, they activate 'kill-me' markers such as ATP, HMGB1 and calreticulin. The immune system recognizes these markers and initiates an anti-tumor response", said Kristin Bedard, VP Research and Development at Kineta. "In turning a cold tumor hot, we believe that Kineta’s RLR agonists can work in synergy with other immuno-therapies like checkpoint inhibitors to potentially enhance efficacy and patient survival."

Kineta, is an emerging and sustainable biotech company that fills a void in the biopharmaceutical industry by efficiently advancing therapies from discovery to clinical proof of concept. We actively collaborate with a broad array of private, government and industry partners to advance our innovative research in chronic pain, immuno-oncology and infectious diseases. Kineta has established and is expanding on a diverse pipeline of novel life improving therapies that address critical unmet patient needs.