December 14, 2021 -- Catamaran Bio has reported preclinical data that demonstrate the capabilities of its Tailwind platform being applied to develop CAT-248, an allogeneic CD70-targeted CAR-NK cell therapy.
Specifically, the data demonstrate successful engineering of a CD70 CAR-NK cell therapy that achieves cytotoxicity in vitro against various tumor cell lines. In addition, the data show highly efficient nonviral delivery of a CAR targeting CD70 and knockout of endogenous CD70 in a single engineering step.
The data, said Catamaran, support advancement of CAT-248, the company'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 American Society of Hematology 2021 meeting in Atlanta.
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 Tailwind platform and characterization of the CD70-targeted CAR-NK cells.
Highlights from the poster include the following:
- CD70 was expressed across hematological and solid tumor malignancies but upregulated in activated peripheral blood NK cells.
- Single-step, nonviral CAR delivery using the TcBuster transposon system and CRISPR-Cas9 editing of NK cells resulted in a more than 70% integration/expression of CD70 CAR and more than an 80% knockout of endogenous CD70.
- Activation of peripheral blood NK cells strongly upregulated CD70 expression, resulting in cancer cell killing upon expression of CD70-directed CAR in these cells.
- A knockout of endogenous CD70-enabled effective expansion of CD70 CAR-NK cells was achieved 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.
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