On November 10, 2022 Catamaran Bio, Inc., a biotechnology company developing off-the-shelf NK cell therapies to treat cancer, reported new data demonstrating preclinical efficacy of two CAR-NK cell therapies in solid and hematological cancers (Press release, Catamaran Bio, NOV 10, 2022, View Source [SID1234623770]). The data are being presented in two posters at the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held in Boston, Massachusetts, November 8-12, 2022.

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"Collectively, these preclinical data sets demonstrate the power of Catamaran’s fully-integrated TAILWIND platform to deliver allogeneic NK cell therapies for solid tumors," said Vipin Suri, PhD, MBA, Chief Scientific Officer of Catamaran Bio. "We have now shown preclinical efficacy in multiple xenograft models with two differentiated CAR-NK cell therapies engineered with the functional attributes necessary for durable efficacy in solid tumors and manufactured using an efficient non-viral cell engineering system."

Data supporting Catamaran’s lead program, CAT-248, will be presented in a poster titled "Engineering CD70-directed CAR-NK cells for the Treatment of Hematological and Solid Malignancies." Highlights include:

The non-viral TcBuster Transposon System was used to deliver transposons containing a CD70 CAR or CD70 CAR/IL15 expression cassette in primary human peripheral blood NK (PBNK) cells.
Knockout of CD70 via CRISPR/Cas9 in CD70 CAR-expressing NK cells mitigated fratricide and increased cell yield.
Engineered cells were highly cytotoxic against multiple CD70-positive tumor cells lines derived from renal cell carcinoma (RCC) and acute myeloid leukemia (AML).
A single dose of engineered NK cells expressing CD70 CAR and secreted IL15 reduced tumor burden and increased survival in an RCC xenograft model, without the need for exogenous IL15.
These results demonstrate the potential for targeting CD70 with CAR-NK cell therapy for the treatment of AML, RCC, and other CD70-positive malignancies while overcoming fratricide issues by engineering with a non-viral transposon delivery system in combination with CRISPR/Cas9 editing.

Data from a second CAR-NK cell therapy construct engineered using the TAILWIND platform are presented in a poster titled "Allogeneic Natural Killer Cells Engineered to Express HER2-directed CAR, Interleukin-15 and TGFβ Dominant Negative Receptor Effectively Control HER2+ Tumors." Highlights include:

The non-viral TcBuster Transposon System enabled high efficiency engineering of a large multi-cistronic cargo containing HER2-CAR, IL15, and TGFβ-DNR. Transposon engineering of CAT-179 resulted in stable expression of the CAR without the need for post-engineering selection.
CAT-179 demonstrated HER2-CAR-driven interferon gamma (IFNγ) production and tumor cell killing in vitro when co-cultured with HER2+ tumor cells.
CAT-179 was resistant to TGFβ-mediated immunosuppression in vitro, indicating that the cells will be protected from TGFβ-mediated immune suppression in the tumor microenvironment.
Engineering of IL15 in CAT-179 significantly enhanced NK cell persistence and in vitro and in vivo and eliminated the need for exogenous cytokine support.
CAT-179 showed potent anti-tumor activity in vivo against a xenografted HER2+ N87 gastric cancer cell line and led to a significant survival benefit in tumor-bearing mice.
These results demonstrate that NK cells engineered via the TAILWIND platform have a favorable pharmacologic profile and the potential for treatment of solid tumors.