Vitamin C2026-05

Vitamin C Conditioning Generates Tumor-Targeting CAR T Cells with Superior Cytotoxicity and Fitness in a Posttransplant Lymphoproliferative Disorder Tumor Model.

Rahmati Pegah, Bonifacius Agnes, Dragon Anna Christina, Malinconico Chiara et al. — Molecular cancer therapeutics

Summary

This study explores how treating specialized immune cells, called CAR T-cells, with vitamin C can enhance their ability to fight cancer. Researchers found that vitamin C improved these cells' capacity to target and destroy cancer cells in lab models of a specific post-transplant cancer. This suggests vitamin C could potentially make this advanced immunotherapy more effective.

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Key points

Treating CAR T-cells with vitamin C improved their ability to kill cancer cells in lab models.
Vitamin C also made these cancer-fighting cells grow better and last longer.
This suggests vitamin C could enhance a type of advanced cancer immunotherapy.
The findings are from laboratory experiments, not human studies.

What the study looked at

What question the study asked: This research investigated whether treating specialized immune cells, known as CAR T-cells, with vitamin C could improve their effectiveness against certain cancers, particularly a type called post-transplant lymphoproliferative disorder (PTLD). How it was studied: Scientists conducted experiments in laboratory settings. They treated CAR T-cells with vitamin C and then tested their performance against cancer cells grown in dishes and in more complex 3D models. These cancer cells were chosen to mimic PTLD, a cancer that can develop after organ transplants. What it found: The study revealed that vitamin C treatment significantly boosted the CAR T-cells' ability to grow, target, and destroy cancer cells. These vitamin C-conditioned cells showed superior killing power and durability compared to untreated cells, suggesting they could be more effective in fighting tumors. The researchers also observed changes in the cells' genetic activity that made them more potent.

Dietary takeaway

This study suggests that vitamin C could play a role in enhancing a specific type of advanced cancer treatment in laboratory settings. However, it's crucial to understand that these findings are from lab models and don't mean that simply increasing your dietary vitamin C intake will have the same effect on cancer. A balanced diet rich in vitamin C from fruits and vegetables remains important for overall health, but this single study does not provide definitive guidance for cancer treatment or prevention through diet.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in hematologic malignancies but faces challenges in solid tumors and virus-associated malignancies such as posttransplant lymphoproliferative disorder (PTLD). Various strategies, including optimization of receptor design, genetic modifications addressing immunomodulatory mechanisms, and refining the manufacturing process, have been explored to overcome limited in vivo persistence and tumor infiltration, antigen escape, and the immunosuppressive tumor microenvironment. This study investigated the effect of vitamin C (vitC) conditioning on CD19-targeting CAR T cells (vitC-CAR19-T) to improve the efficacy of CAR T-cell therapy. VitC has been shown to influence immune responses through epigenetic regulation and oxidative stress reduction. Enhanced transduction efficiency and proliferative capacity by vitC conditioning resulted in a higher yield of CD4+ and CD8+ CAR19-Ts. VitC-CAR19-Ts exhibited faster and improved cytotoxic response toward CD19+ Nalm-6 cells and Epstein-Barr virus-infected B-lymphoblastoid cell lines, the in vitro model of PTLD. Increased demethylation was observed in TBX21 regions, which was in line with a type 1-like phenotype and higher expression of effector molecules such as granulysin in both CD4+ and CD8+ in vitC-CAR19-Ts, providing insights into the effects of vitC conditioning. Importantly, vitC-CAR19-Ts outperformed CAR19-Ts in long-term antigen stress assays and three-dimensional multicellular spheroid models, indicating a potentially improved in vivo functionality and tumor infiltration capacity. In summary, vitC conditioning represents a promising strategy to enhance CAR T-cell yield, cytotoxic potential, and durability, complementing existing approaches to overcome the limitations of CAR T cells in the treatment of hematologic malignancies and solid tumors.

View on PubMed →DOI: 10.1158/1535-7163.MCT-25-0005