Potential colon carcinoma cure

Small-molecule compounds demonstrate tumor regression and adaptive immune response

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SEATTLE—Kineta Inc., a biotechnology company focused on the translational development of novel therapies in immuno-oncology, presented on a paper on the discovery and characterization of small-molecule compounds that appear to provide adaptive immune response and tumor regression on March 22 at the Keystone Symposia on Molecular and Cellular Biology conference titled Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology.
Kineta is a sustainable biotech company that advances therapies from discovery to clinical proof of concept and actively collaborates with private, government and industry partners to advance research in chronic pain, immuno-oncology and infectious diseases.
The “hit to lead” small-molecule compounds 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, according to the company. Additionally, mice in the study that demonstrated complete tumor regression to initial drug treatment were resistant to tumor re-challenge, confirming an adaptive immune response in these animals.
As Kineta CEO Shawn Iadonato explained, “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. These data are groundbreaking in cancer immuno-therapy as we successfully established tumor immunity in mice that had complete regression to an initial tumor.”
He added that 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 (ICD) in the CT26 colon carcinoma model. Inducing ICD in tumor cells results in the release of danger signals including ATP, HMGB1 and calreticulin that eventually enhance immune recognition of the tumor.
According to Kristin Bedard, vice president of research and development at Kineta, “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 antitumor response. 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 just unveiled its immune-oncology program in October. Around that time, Iadonato joined a panel of leaders from other biopharmaceutical companies to discuss novel new treatment strategies in immuno-oncology. The panel presentation entitled “The Intersection of Inflammation and Immuno-Oncology: Risks and Opportunities” was conducted at the 15th annual BIO Investor Forum in San Francisco.
Iadonato highlighted details around Kineta’s small-molecule compounds that may activate the RIG-I pathway to elicit immunogenic cell death in cancer tumor models. These novel compounds were identified using Kineta’s proprietary AViiD screening platform, which has also identified innate immune antivirals and vaccine adjuvants.
“Cancer is typically not recognized as foreign by the body’s immune system, which allows tumors to grow unchecked,” Iadonato explained. “Kineta’s immune modulators activate the RIG-I pathway and may reprogram the immune system to recognize tumors as foreign and elicit neo-antigen T cell responses to kill cancer. Priming the tumor microenvironment may also enable other therapies to be more effective when used in combination.”
In recent news of other therapeutic areas for Kineta, the company presented a talk at the 9th Annual Biotech Showcase Investor Conference in San Francisco in January. Iadonato provided an overview of the company and KCP-400, a novel non-opioid in preclinical development for the treatment of chronic pain. He outlined the robust analgesic, anti-inflammatory and neuroprotective effects that have been demonstrated in multiple pain models with this first-in-class therapeutic.

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