– Two poster presentations at ASGCT Annual Meeting demonstrate potential of synthetic receptors to prevent TGFβ-mediated immunosuppression and enhance NK cell expansion and function –
CAMBRIDGE, Mass. – May 16, 2022 – Catamaran Bio, Inc., a biotechnology company developing off‑the-shelf chimeric antigen receptor (CAR)-NK cell therapies to treat cancer, is presenting new preclinical data today at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, being held in Washington, DC. The data demonstrate successful engineering of CAR-NK cells to preserve and enhance NK cell activity in the immunosuppressive tumor microenvironment.
“The ability to enable robust functioning of CAR-NK cells in the immunosuppressive solid tumor microenvironment will be critical to the success of cell therapies,” said Vipin Suri, PhD, MBA, Chief Scientific Officer of Catamaran Bio. “We are presenting data on a TGFβ receptor that lacks an intracellular signaling domain and acts as a TGFβ trap, as well as proprietary next generation switch receptors that reconfigure inhibitory TGFβ signaling to be stimulatory. Both approaches lead to protection from TGFβ immunosuppression of CAR-NK cells as well as neighboring immune cells. The approaches we are presenting at ASGCT are part of our innovative switch receptor platform which includes multiple strategies to convert other immunosuppressive signals into beneficial signals that stimulate and enhance the therapeutic activity of NK cells.”
Highlights of the data presented on TGFβ switch receptors for CAR-NK cell therapies are as follows:
Abstract #313: Dominant Negative Receptor for TGFβ
A TGFβ dominant negative receptor (DNR) was shown to protect the function of both the engineered CAR‑NK cells and neighboring NK cells from the immunosuppressive effects of TGFβ.
- CAR-NK cells engineered with this TGFβ DNR demonstrated reduction of downstream TGFβactivity as shown by >90% reduction of SMAD2 phosphorylation (a downstream signal of TGFβ activity) even at supraphysiological doses of TGFβ.
- By acting as a sink, the TGFβ DNR also protected neighboring NK cells from immunosuppressive TGFβ signaling, resulting in approximately a 3-fold reduction in potency of TGFβ in inducing SMAD2 phosphorylation.
- Co-expression of the TGFβ DNR with a HER2-CAR construct restored CAR-dependent cytotoxicity in the presence of TGFβ.
Abstract #331: Next Generation TGFβ Switch Receptors
Building on its success using TGFβ-DNRs to prevent immunosuppression, Catamaran also engineered synthetic receptors that effectively converted TGFβ signals into cell stimulatory signals.
- A diverse set of switch receptors were engineered with a TGFβ receptor extracellular domain, coupled with various intracellular domains.
- These proprietary next generation TGFβ switch receptors successfully reversed TGFβ-mediated inhibition, promoted NK cell expansion in vitro, and enhanced NK cell functional responses.
- Chronic TGFβ stimulation strengthened NK cell tumor killing and target-induced cytokine secretion, and incorporation of the switch receptors also protected the cells from suppressive TGFβ signaling.
The posters will be available on the Catamaran Bio website.
About Catamaran Bio
Catamaran Bio is developing novel, off-the-shelf chimeric antigen receptor (CAR)-NK cell therapies designed to treat a broad range of cancers, including solid tumors. Our proprietary capabilities enable us to harness the natural cancer-fighting properties of NK cells and enhance and tailor their effectiveness with the power of synthetic biology and innovative non-viral cell engineering. We are using our TAILWIND™ platform, an integrated suite of technologies, to specifically address the end-to-end methods of engineering, processing and manufacturing NK cells and rapidly advance our pipeline of CAR-NK cell therapy programs. Our team combines experienced biopharmaceutical leadership with founding scientists who are pioneers in NK cell biology, engineering, manufacturing, and clinical application. Catamaran is backed by leading financial and corporate investors, including SV Health Investors, Sofinnova Partners, Lightstone Ventures, Takeda Ventures, Astellas Venture Management, and the UMN Discovery Capital investment program. For more information, please visit www.catamaranbio.com and follow us on LinkedIn and @CatamaranBio on Twitter.
Mark Boshar, Chief Operating Officer
Kathryn Morris, The Yates Network