Candel Therapeutics' (NASDAQ: CADL) enLIGHTEN Discovery Platform Aims To Tackle Complexities Of Tumor Microenvironments

Candel Therapeutics, Inc. CADL is helping pioneer the next generation of viral immunotherapy by leveraging a data-driven approach to create new assets and further the development of existing drug candidates.

Candel Therapeutics' enLIGHTEN Discovery Platform integrates artificial intelligence-selected, therapeutic payloads into programmable vectors for delivery into the tumor microenvironment

This tailored approach to discovery and development of new therapeutics has been designed to address the complexity of the tumor microenvironment and the diversity of the tumor response to existing treatments. 

Using large patient datasets, the enLIGHTEN™ Discovery Platform identifies druggable properties that correlate with clinical outcomes and predicts optimal therapeutic payload combinations in silico. Real-world testing of these predicted payload combinations is used to rapidly evaluate their therapeutic effects. Next, validated multigene payloads are integrated into one of Candel's programmable viral vectors that are engineered with tunable features to address a specific unmet need in cancer treatment.

The enLIGHTEN™ immunotherapy candidates represent a novel class of bespoke immunotherapies with each one tailored for a specific indication, disease stage, or rationally designed therapeutic combination therapy. 

First Experimental Candidate

During the Society for Immunotherapy of Cancer (SITC) 2023 Annual Meeting and the International Oncolytic Virus Conference in November 2023, Candel presented the first experimental immunotherapy candidate from its discovery platform: Alpha 201-macro-1, an investigational,viral immunotherapy designed to activate innate immune surveillance. Preclinical data demonstrated that programmable, vector-mediated delivery of a novel gene payload designed to interfere with the CD47/SIRPα pathway significantly impede tumor growth when compared to systemic anti-CD47 antibody therapy in a mouse model of breast cancer. 

Soon afterwards, at the American Association for Cancer Research (AACR) Annual Meeting in April 2024, the company presented late-breaking data from its second immunotherapy candidate based on this platform: a therapeutic able to induce organized lymphocyte aggregates that resemble tertiary lymphoid structures (TLS) within solid tumors. Formation of TLS in tumors correlates with a positive response to immune checkpoint inhibitors and better prognosis. To date, there has not been any drug able to induce therapeutic TLS formation in cancer. 

The effects of Candel's new immunotherapy candidate are based on two mechanisms. First, profiling of the biological response to the enLIGHTEN™ programmable vector demonstrated its potential to orchestrate changes in the tumor microenvironment, which bolster effective anti-tumor immune responses to immune checkpoint inhibitor treatment. Second, delivery of two unique payload combinations using this programmable vector resulted in TLS formation associated with monotherapy anti-tumor activity, and enhanced responses in combination with immune checkpoint inhibitor treatment in mouse models of solid tumors. Combining the immunological and oncolytic effects mediated by the viral vector with the biological activity of the transgene payloads results in a unique multimodal therapeutic able to induce the formation of TLS and inhibit the tumor.

"With the enLIGHTEN Discovery Platform, we are leveraging our internal expertise and capabilities to design a new class of multimodal therapeutics that can overcome mechanisms of resistance present in the tumor microenvironment and address critical unmet needs for patients with cancer," said Francesca Barone, M.D. Ph.D., CSO at Candel Therapeutics. "This platform has been designed for collaborations focused on rational combination therapies to induce disease remission in cancer. " 

More exciting developments are on the horizon. Candel Therapeutics and the University of Pennsylvania are collaborating in a discovery partnership that will leverage enLIGHTEN™ programmable vectors with therapeutic payloads to potentially overcome barriers to Chimeric antigen receptor (CAR) T-cell therapies. Through the partnership, the University of Pennsylvania researchers – led by the Director of the T-Cell Engineering Lab within Penn's Center for Cellular Immunotherapies, Neil C. Sheppard, Ph.D.  – will explore the ability of Candel's novel viral immunotherapies to enhance the effects of the university's CAR T-cell therapies in solid tumor models.  

Featured photo by National Cancer Institute on Unsplash

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