On December 13, 2021 Catamaran Bio, Inc., a biotechnology company developing off-the-shelf chimeric antigen receptor (CAR)-NK cell therapies to treat cancer, reported preclinical data that demonstrate key capabilities of its TAILWINDTM platform being applied to develop CAT-248, an allogeneic CD70-targeted CAR-NK cell therapy (Press release, Catamaran Bio, DEC 13, 2021, View Source [SID1234596967]). The data demonstrate successful engineering of a CD70 CAR-NK cell therapy that achieves cytotoxicity in vitro against various tumor cell lines. Using the integrated engineering and manufacturing capabilities of the TAILWIND platform, the data also show highly efficient non-viral delivery of a CAR targeting CD70 and knock out of endogenous CD70 in a single engineering step.
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The data support advancement of CAT-248, Catamaran’s co-lead CAR-NK cell therapy candidate, which is directed against CD70, a tumor antigen that is highly expressed on certain types of cancers including renal cell carcinoma, glioma, pancreatic cancer, and acute myeloid leukemia. The results were presented at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) being held in Atlanta from December 11-14, 2021.
"CD70 is a compelling target in several high unmet need solid tumors and hematologic malignancies and we are excited to support the advancement of CAT-248 as an effective therapy for CD70 expressing cancers," said Alvin Shih, MD, MBA, Chief Executive Officer of Catamaran Bio. "These data further establish our TAILWIND platform as an industry-leading, highly versatile and scalable manufacturing platform for CAR-NK cell therapies, including complex products with multiple genome modifications."
"Our ASH (Free ASH Whitepaper) data demonstrate cutting-edge capabilities that are essential for both tumor-targeting design as well as scalable manufacturing of CAR-NK cell therapies," said Vipin Suri, PhD, MBA, Chief Scientific Officer of Catamaran Bio. "Notably, we have now demonstrated a novel single-step engineering approach for simultaneously using a non-viral transposon system for CAR delivery in combination with CRISPR editing for gene knockout. Using our TAILWIND platform, we effectively integrate all the necessary properties to position our CAR-NK cells as allogeneic, off-the-shelf therapies for multiple cancers, especially solid tumors."
Data presented in a poster titled, "Engineering CD70-Directed CAR-NK Cells for the Treatment of Hematological and Solid Malignancies," describe experiments showing key capabilities of the TAILWINDTM platform and characterization of the CD70-targeted CAR-NK cells. Highlights from the poster include:
CD70 was expressed across hematological and solid tumor malignancies but upregulated in activated peripheral blood NK cells.
Single-step, non-viral CAR delivery using the TcBusterTM Transposon System and CRISPR/Cas9 editing of NK cells resulted in more than 70% integration/expression of CD70 CAR and more than 80% knockout of endogenous CD70.
Activation of peripheral blood NK cells strongly upregulated CD70 expression, resulting in fratricide upon expression of CD70 directed CAR in these cells.
Knockout of endogenous CD70 enabled effective expansion of CD70 CAR-NK cells while maintaining innate cytotoxicity.
CAR-NK cells engineered with CD70 CAR and CRISPR/Cas9 knockout of endogenous CD70 were active against multiple CD70‑positive tumor lines.
The studies presented at ASH (Free ASH Whitepaper) are co-authored by Catamaran and its collaborators at the University of Minnesota. The poster presentation is available on Catamaran’s website.