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Jul 30, 2025, 09:51

Michael Jain: Comparative Analysis of Two CD19 CAR T Cell Products Using Single-Cell RNA Sequencing

Michael Jain, Oncologist at Moffitt Cancer Center, shared a post on X about recent paper by Xiaoqing Yu et al., published in JITC.

“Our manuscript using single cell RNA sequencing to compare two CD19 CAR T cell products, axi-cel and tisa-cel is online at JITC!

Clinically, axi-cel is more effective than tisa-cel but has more CRS and ICANS toxicities. We found that the infusion product of axi-cel has more central memory cells, whereas tisa-cel was more proliferative at the time it was received for patient infusion.

We were able to compare T cells that had the CAR (CAR+) inserted to T cells that did not (CAR-). For axi-cel, the gene expression of the CAR+ cells was very different than that of the CAR- cells. Unexpectedly, for tisa-cel CAR+ and CAR- cells were nearly identical.

In vitro, we found that CAR T cells became less central memory and more proliferative, and the CAR+ and CAR- cells more similar, the longer they were left in culture. Thus, a lot of the phenotype of tisa-cel was probably driven by the longer manufacturing time for tisa-cel.

We also looked at axi-cel characteristics associated with durable response. We did not find that any cluster (or T cell subtype) associated with outcome. Instead, having high Myc expression and ribosomal synthesis genes across clusters was associated with good outcome.

Thus our study is a resource for others, and we think good CAR T quality comes from cells that have divergent CAR+ and CAR- cells, and healthy protein synthesis/secretory pathways. Thanks to the Locke Lab, and Xiaoqing Yu and the Bioinformatics Core at Moffitt.”

Title: Comparison of axicabtagene ciloleucel and tisagenlecleucel patient CAR-T cell products by single-cell RNA sequencing

Authors: Xiaoqing Yu, Michael D. Jain, Meghan A. Menges, Ling Cen, Jerald D. Noble, Reginald Atkins, Turab J. Mohammad, Christina A. Bachmeier, Samira Naderinezhad, Kayla Reid, Salvatore Corallo, Sean J. Yoder, Chaomei Zhang, Lanmin Zhang, Julieta Abraham Miranda, Bijal Shah, Julio C. Chavez, Rebecca S. Hesterberg, Luis Cuadrado Delgado, Constanza Savid-Frontera, Paulo C. Rodriguez, John L. Cleveland, Xuefeng Wang, Marco L. Davila, Frederick L. Locke.

Read The Full Article at JITC.

Michael Jain: Comparative Analysis of Two CD19 CAR T Cell Products Using Single-Cell RNA Sequencing

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Michael Jain: Comparative Analysis of Two CD19 CAR T Cell Products Using Single-Cell RNA Sequencing