Senti Bio Announces New Advances in Next-Generation CAR-NK Therapy to Challenge AML Early data are encouraging

Article source: Medicine Cube Pro

Author: Bai Lu

While engineered cell therapy has revolutionized the treatment of blood cancers, for some types of cancer, precisely selecting the right targets to kill cancer cells while sparing healthy cells remains a challenge

Now, SENTI-202, an off-the-shelf CAR-NK cell therapy for AML developed by Senti Bio, has received promising early data

Specifically, to maximize AML tumor clearance and reduce extra-tissue toxicity, Senti leveraged a proprietary bioinformatics paired antigen discovery platform to identify targeting of AML tumor-associated antigens using an OR and NOT logic-gated CAR gene circuit approach and the optimal combination of healthy tissue antigens

In vitro studies have shown that FLT3 OR CD33 CAR-NK cells are superior to FLT3 or CD33 single-target CAR-NK cells in killing cancer in several leukemia cell lines

For the NOT logic-gated component designed to reduce off-target toxicity, the team selected a surface antigen, EMCN, which is expressed on up to 76% of healthy HSCs but not on AML cells

In vitro studies showed that an EMCN-specific inhibitory CAR protected up to 67% of cells expressing both FLT3 and EMCN from accidental injury by the FLT3-targeted activating CAR

The researchers also mixed FLT3 cells with cells expressing or not expressing EMCN to mimic healthy cells and AML cells

The SENTI-202 CAR-NK data presented at the ASH meeting, the first complete proof-of-concept dataset for Senti's OR and NOT-gated gene circuits, supports the technology's potential for "enhanced targeting of a broader spectrum of cancers while limiting off -tumor toxicity" idea

SENTI-202 is one of the first projects to appear on the SENTI platform

The gene-circuit technology has already attracted interest from Big Pharma

References:

1# ASH: Senti Bio's gene circuit CAR-NK cell therapy enhances cancer killing and safety in leukemia models (Source: FIERCE Biotech)

2# 2799 FLT3 OR CD33 NOT EMCN Logic Gated CAR-NK Cell Therapy (SENTI-202) for Precise Targeting of AML (Source: ASH)