biostudies-literatureKostopoulos NNCI NIH HHS6308-6320https://www.ebi.ac.uk/biostudies/studies/S-EPMC11700247biostudies-literatureUnknown8(24)<h4>Abstract</h4>Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CART-19) represents a significant advance in the treatment of patients with relapsed or refractory CD19+ B-cell lymphomas. However, a significant portion of patients either relapse or fail to respond. Moreover, many patients have symptomatic disease, requiring bridging radiation therapy (RT) during the period of CAR T-cell manufacturing. To investigate the impact of 1 to 2 fractions of low-dose RT on CART-19 treatment response, we developed a mouse model using A20 lymphoma cells for CART-19 therapy. We found that low-dose fractionated RT had a positive effect on generating abscopal systemic antitumor responses beyond the irradiated site. The combination of RT with CART-19 therapy resulted in additive effects onBlood advancesLocal radiation enhances systemic CAR T-cell efficacy by augmenting antigen crosspresentation and T-cell infiltration.PMC11700247R01 CA206012Facciabene AThyfronitis GLaRiviere MJChong EAKoumenis CBeghi SSchuster SJKrimitza EKostopoulos NCostabile FGoia DPerales-Linares RPlastaras JPMaity AfalseLocal radiation enhances systemic CAR T-cell efficacy by augmenting antigen crosspresentation and T-cell infiltration.<h4>Abstract</h4>Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CART-19) represents a significant advance in the treatment of patients with relapsed or refractory CD19+ B-cell lymphomas. However, a significant portion of patients either relapse or fail to respond. Moreover, many patients have symptomatic disease, requiring bridging radiation therapy (RT) during the period of CAR T-cell manufacturing. To investigate the impact of 1 to 2 fractions of low-dose RT on CART-19 treatment response, we developed a mouse model using A20 lymphoma cells for CART-19 therapy. We found that low-dose fractionated RT had a positive effect on generating abscopal systemic antitumor responses beyond the irradiated site. The combination of RT with CART-19 therapy resulted in additive effects on2024-01-01T00:00:00Z2024 Dec2026-06-01T23:13:15.814Z2026-05-23T03:08:08.636ZS-EPMC117002473921342210.1182/bloodadvances.2024012599