Carl June's latest Cell: CAR-T treatment of solid tumors key new targets-ID3 and SOX4

Article source: Medical Rubik's Cube Pro

Author: Manhua

Since the first CAR-T therapy was launched in 2017, 5 CD19 CAR-T and 1 BCMA CAR-T therapy have been approved worldwide.

The phenomenon of T cell depletion is thought to have evolved to prevent these powerful immune cells from causing too much collateral damage to the body

In a study published in Cell on December 2, a team of scientists from the Perelman School of Medicine at the University of Pennsylvania revealed the key molecular mechanism of the CAR-T depletion process and pointed out potentially effective strategies to overcome the depletion process.

Source: Cell

In the study, Professor Carl H.

CD8+ T cells transform to NK-like T cells under continuous antigen stimulation (Source: Cell)

Specifically, they designed a mesothelin to target CAR-T cells and exposed the CAR-T cells to mesothelin-expressing pancreatic tumor cells for 4 weeks

ID3 and SOX4 are potential regulators of dysfunction (exhaustion) characteristics (Source: Cell)

More importantly, the researchers observed that the depletion of CAR-T cells was accompanied by a surge in the levels of two proteins, ID3 and SOX4, which are the master switches of a large number of genes in immune cells

Destruction of ID3 and SOX4 improves the effector function of CAR-T (Source: Cell)

In summary, this study reveals the plasticity of human CAR-T cells and proves that down-regulating the expression of ID3 and SOX4 can improve the efficacy of CAR-T cells in the treatment of solid tumors by preventing or delaying CAR-T cell dysfunction

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Reference materials:

[1] Charly R.

[2] New insights into T cell exhaustion could improve cancer immunotherapies, study finds (Source: Perelman School of Medicine at the University of Pennsylvania)