2024.06.12 Boosting CAR-T cell therapies from under the skin

Manuscript title: Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of preadministered CAR-T cells Journal: Nature Biomedical Engineering Publication date: paper was published on 6/3/24 T-cell enhancing scaffold illustration: Image 1 caption: T-cell enhancing scaffolds can be locally injected under the skin following CAR-T cell therapy, and allow circulating CAR-T cells to infiltrate their 3-dimensional porous scaffold structure. There, CAR-T cells become activated and are induced to proliferate before they eventually egress into the blood circulation to carry out systemic antitumor functions. As shown on the right, TES release the interleukin IL-2, which stimulates CAR-T cells to multiply, and anti-CD3 and anti-CD28, two antibodies that, similar to tumor antigens presented by an antigen-presenting cell (APC) of the immune system, stimulate CAR-T cells to differentiate into tumor cell-killing “effector T cells.” Credit: Wyss Institute at Harvard University Vacscularized TES under the skin: This image shows a TES (in blue) 21 days following its injection under the skin of a mouse, including small blood vessels that connect it with the blood system Credit: Wyss Institute at Harvard University CAR-T cells in TES: 14 days following their injection under the skin of lymphoma-bearing mice, TES loaded with the T-cell activating factor IL-2 and T-cell receptor stimulating antibodies anti-CD3 and anti-CD28 contain significantly more CAR-T cells (stained in green), compared to blank TES lacking the three factors. Credit: Wyss Institute at Harvard University