GD2-CART

Dual blockade of TIGIT and programmed death-1 (PD-1) increased the cytotoxicity of GD2-CARTs to some extent, suggesting that low TIGIT and PD-1 expression of GD2-CARrejTs is a major factor required for robust cytotoxicity against SCLC. Not only for robust cytotoxicity but also for availability as "off-the-shelf" T cell therapy, iPSC-derived GD2-CARrejTs are a promising novel treatment for SCLC.

Longitudinal analysis of post-treatment samples identified increased CXCR3 classical monocytes in all groups as CAR-T numbers waned. Together, our data uncover mediators of CAR-T biology and correlates of expansion that could be utilized to advance immunotherapies for solid tumor patients.

Our work provides a novel platform to perform guided CAR insertion into primary human T-cells using nanoplasmid DNA and holds the potential to increase access to CAR-T cell therapies.

CXCR3 has been extensively studied on T cells, but its function on myeloid populations is yet to be fully explored. These results are the first to demonstrate that the peripheral immune environment prior to CAR-T administration may effectively predict and modulate CAR-T expansion in patients.

H3K27M-mutated DIPG/DMG patients demonstrate continued clinical response with serial ICV GD2 CAR-T infusions, with heterogeneity in the durability of response across patients. In-depth correlative analyses profile distinct immune populations and demonstrate population shifts depending on route of administration and over the course of treatment. Key findings from these data will allow for iterative improvement in CAR-T therapies for H3K27M+ DIPG/DMG patients, providing hope to shift the paradigm of this fatal disease.