eBook: Breakthroughs and Innovations in Immunology Research - 23

tions. Nonetheless, CAR-NKs exhibit lower potency
and persistence than CAR-T cells, which may limit
their efficacy against certain cancers. In addition,
although the shorter half-life of NK cells can reduce
the risk of on-target/off-tumor toxicity to normal
cells, it can contribute to poor cytotoxicity in an immunosuppressive
TME.
Generating sufficient NK cells is essential for adoptive
immunotherapy, and cytokines such as IL-2,
IL-7, IL-12, IL-15, and IL-21 are critical for in vivo
growth and survival of NK cells. Sino Biological has
successfully developed high-purity, high-activity
GMP- grade cytokines to aid in the development
of human adoptive immunotherapies.
CAR-M
In contrast to T and NK cells, macrophages possess
the ability to infiltrate and persist within tumors.
They also exhibit a distinct mechanism of tumor
cell killing: phagocytosis. CAR-M and the more
recent CAR-M derived from induced pluripotent
stem cells (CAR-iMac) are emerging alternatives to
conventional CAR-T therapy.
The core components of CAR-M are similar to CAR-T,
including an extracellular domain that provides
specific
recognition via a single-chain variable
fragment (scFv), such as CD19 or HER2, a hinge domain,
a transmembrane domain (mainly CD8), and
an intracellular domain for dedicated downstream
signaling, such as CD3z and FcgR. (Figure 4)
Similar
to other CAR-based immunotherapies,
CAR-M faces challenges from antigen loss and cytokine
toxicity. However, CAR-M has several advantages
over CAR-T and CAR-NK, such as superior immune
cell trafficking, TME infiltration, and the ability
to overcome immunosuppressive TMEs. Tumor-asFigure
4. The structures of various generations of CAR-Ms that differ in their intracellular domain. Source: adapted from Wang Sh, et al. 2022
23

eBook: Breakthroughs and Innovations in Immunology Research

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