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R. Orentas

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Open access Jul 2026

Spatial tissue analysis of secondary sarcoma following CAR T cell therapy for B cell lymphoma

Summary CD19-directed chimeric antigen receptor (CAR)-engineered T cells have transformed cellular therapy for hematologic malignancies but have also raised concerns about secondary malignancies. A spatial profiling method was used to analyze the tumor microenvironment and define native and CAR T cell association with a pleomorphic sarcoma arising 12 months post-CAR T therapy for B cell lymphoma. Although CAR T sequences were absent in the secondary tumor, our approach enabled profiling of the stroma, tumor, and infiltrating T cells. Spatial analysis incorporated proteomics via serial antibody staining and transcriptomics using RNA hybridization on an automated MACSima imaging cyclic staining (MICS) system, which allows for in situ detection of CAR T cells. We report here the prevalence of CAR-positive T cells in patient-derived tissue sections, observed metabolic and proliferative shifts in the tumor and its microenvironment, and immune checkpoint analysis. These findings provide insights into post-CAR T secondary cancers and highlight tools that may guide future targeted therapies.

Jia-Jye Lee, Peirong Hu, Kun Luo et al. · 0 citations
Open access Jul 2026

CAR-T with ICOS costimulation lacks therapeutic efficacy in patients due to strong trogocytosis and failure of expansion 2261203

The ICOS domain promotes trogocytosis and fratricide, explaining the poor persistence and function of ICOS CAR-T cells observed in this trial and raise significant caution for using CAR constructs that rely on ICOS for CAR activation.

Yongxia Wu, Allison Pugel, Katie A. Palen et al. · 0 citations
Jul 2026

Safety and clinical outcomes of a first-in-human trial of point-of-care manufactured trispecific CAR T cells targeting CD19, CD20, and CD22.

A trispecific CAR targeting CD19, CD20, and CD22 with OX40 co-stimulatory domain with overall response rate was 50%, including complete responses in 83% of lymphoma patients, and one-year overall survival rate was 61%, with durable remissions observed in lymphoma.

S. Vasu, N. Denlinger, No-Joon Song et al. · 0 citations
Open access Jul 2026

Development of a 3-day manufacturing method to generate CD19-CD20-CD22 trispecific CAR T-cells from whole blood

Compared to the standard 7-day method, the 3-day approach resulted in expression of genes associated with a more stem-like phenotype while reducing manufacturing time and cost, and may provide a practical alternative for decentralized CAR T-cell manufacturing, particularly in resource-limited settings.

Isabella Vignola, M. Procházková, L. Shao et al. · 1 citation