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CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity
Naveen K Mehta1, Kavya Rakhra1, Kristan A Meetze1
1Cullinan Therapeutics, Inc., Cambridge, Massachusetts.
Cancer Immunology Research
|June 6, 2024
Summary
A novel fusion protein, CLN-617, co-delivers interleukin 2 (IL2) and interleukin 12 (IL12) intratumorally. This therapy eradicated tumors and enhanced anti-PD1 efficacy in preclinical models, offering a promising cancer treatment.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Cytokine therapies like IL2 and IL12 show antitumor potential but face challenges with toxicity and efficacy.
- Existing IL2 therapy has limited clinical use due to systemic toxicities, and IL12 lacks approval because of severe dose-limiting toxicities.
Purpose of the Study:
- To develop a novel, first-in-class therapeutic agent, CLN-617, for intratumoral injection that safely and effectively co-delivers IL2 and IL12.
- To evaluate the antitumor activity and immune-modulating effects of CLN-617 in preclinical cancer models.
Main Methods:
- Development of CLN-617, a single-chain fusion protein combining IL2, IL12, LAIR2, and HSA for enhanced retention.
- Administration of a murine surrogate (mCLN-617) via intratumoral injection in syngeneic tumor models.
- Assessment of tumor eradication, abscopal effects, and synergy with anti-PD1 checkpoint therapy.
Main Results:
- Intratumoral administration of mCLN-617 led to the eradication of both treated and untreated tumors.
- CLN-617 significantly enhanced the response rate when combined with anti-PD1 checkpoint therapy.
- A robust abscopal response was observed, dependent on cellular immunity and antigen cross-presentation.
Conclusions:
- CLN-617 represents a novel approach to cytokine therapy, overcoming limitations of previous IL2 and IL12 treatments.
- The fusion protein demonstrates potent antitumor activity and immune stimulation, supporting its clinical evaluation.
- CLN-617 is currently under investigation in a clinical trial for advanced solid tumors.
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