iPSC-derived CAR platforms

Early-phase clinical studies such as CT-0508 demonstrate feasibility and tumor-microenvironment remodeling with CAR-MΦ.

Early-phase clinical studies (e.g., CT-0508) demonstrate feasibility and TME remodeling with CAR-MΦ.

CAR-NK and CAR-MΦ have emerged as promising innate immune alternatives to conventional CAR-T cells for solid tumors.

innate immune cell platforms, particularly chimeric antigen receptor-engineered natural killer (CAR-NK) cells and chimeric antigen receptor-macrophages (CAR-MΦ), have emerged as promising alternatives

Recent CAR-NK and CAR-MΦ advances include lineage-specific intracellular signaling domains, novel effector constructs, and scalable iPSC-derived platforms.

We highlight key innovations, including the use of lineage-specific intracellular signaling domains (e.g., DAP12, 2B4, FcRγ), novel effector constructs (e.g., NKG7-overexpressing CARs, TME-responsive CARs), and scalable induced pluripotent stem cell (iPSC)-derived platforms.

Dual-effector regimens, cytokine-modulated cross-support, and bispecific or logic-gated CARs may overcome current barriers and provide more durable, tumor-selective responses.

Emerging combinatorial strategies, such as dual-effector regimens (CAR-NK+ CAR-MΦ), cytokine-modulated cross-support, and bispecific or logic-gated CARs, may overcome these barriers and provide more durable, tumor-selective responses.

Persistent challenges for CAR-NK and CAR-MΦ include transient in vivo survival, manufacturing complexity, and risks of off-target inflammation.

However, persistent challenges remain, including transient in vivo survival, manufacturing complexity, and risks of off-target inflammation.

Preclinical data support enhanced antitumor activity of CAR-NK and CAR-MΦ through MHC-unrestricted cytotoxicity, phagocytosis, trogocytosis, cytokine secretion, and cross-talk with adaptive immunity.

Preclinical data support enhanced antitumor activity through mechanisms such as major histocompatibility complex (MHC)-unrestricted cytotoxicity, phagocytosis, trogocytosis, cytokine secretion, and cross-talk with adaptive immunity.

Recent CAR-NK and CAR-MΦ advances include lineage-specific intracellular signaling domains, novel effector constructs, and scalable iPSC-derived platforms.

We highlight key innovations, including the use of lineage-specific intracellular signaling domains (e.g., DAP12, 2B4, FcRγ), novel effector constructs (e.g., NKG7-overexpressing CARs, TME-responsive CARs), and scalable induced pluripotent stem cell (iPSC)-derived platforms.

Source: Engineering Innate Immunity: Recent Advances and Future Directions for CAR-NK and CAR-Macrophage Therapies in Solid Tumors.