B7-H3 CAR-T cell therapy combined with irradiation is effective in targeting bulk and radiation-resistant chordoma cancer cells.

Background: Chordoma is a slow-growing, primary malignant bone tumor that arises from notochordal tissue in the midline of the axial skeleton. Surgical excision with negative margins is the mainstay of treatment, but high local recurrence rates are reported even with negative margins. High-dose radiation therapy (RT), such as with proton or carbon ions, has been used as an alternative to surgery, but late local failure remains a problem.

A multi-kinase inhibitor screen identifies inhibitors preserving stem-cell-like chimeric antigen receptor T cells.

Chimeric antigen receptor T cells (CAR T cells) with T stem (T) cell-like phenotypic characteristics promote sustained antitumor effects. We performed an unbiased and automated high-throughput screen of a kinase-focused compound set to identify kinase inhibitors (KIs) that preserve human T cell-like CAR T cells. We identified three KIs, UNC10225387B, UNC10225263A and UNC10112761A, that combined in vitro increased the frequency of CD45RACCR7TCF1 T cell-like CAR T cells from both healthy donors and patients with cancer.

Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers.

Interleukin-15 (IL-15) promotes the survival of T lymphocytes and enhances the antitumour properties of chimeric antigen receptor (CAR) T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy. Glypican-3 (GPC3) is expressed in a group of solid cancers, and here we report the evaluation in humans of the effects of IL-15 co-expression on GPC3-expressing CAR T cells (hereafter GPC3 CAR T cells). Cohort 1 patients ( NCT02905188 and NCT02932956 ) received GPC3 CAR T cells, which were safe but produced no objective antitumour responses and reached peak expansion at 2 weeks.

Macrophages producing chondroitin sulfate proteoglycan-4 induce neuro-cardiac junction impairment in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is caused by the absence of the full form of the dystrophin protein, which is essential for maintaining the structural integrity of muscle cells, including those in the heart and respiratory system. Despite progress in understanding the molecular mechanisms associated with DMD, myocardial insufficiency persists as the primary cause of mortality, and existing therapeutic strategies remain limited. This study investigates the hypothesis that a dysregulation of the biological communication between infiltrating macrophages (MPs) and neurocardiac junctions exists in dystrophic cardiac tissue.