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Strengthening the survival of T cell cells to improve the treatment with solid tumor

healthtostBy healthtostJune 13, 2025No Comments4 Mins Read
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Marcela Maus, MD, PhD, director of the Cellular Immunotherapy program and Paula J. O’Kefeffe have resulted in president of General Cancer Center, is a senior author and Stefanie Bailey, PhD, Hana Takei and Giulia Escobar, PhD of the MassachUSets Family Center, Car-T CD28 cells show increased survival, efficiency and resistance to multiple mouse volume models. ”

Q: How would you summarize your study for an audience?

Chimeric antigen cells (CAR) -T are a very promising cancer treatment made by the patient’s T cells, which are reprogrammed to fight their cancer. One of the limitations of the treatment with car-t cells is the ability of these cells to survive enough to target the entire tumor.

Once injected back into the patient, Car-T cells tend to extend rapidly when activated by tumor cells, but eventually die due to a natural process called an activation cell death.

We have discovered a way to change Car-T cells so that they can partially avoid the cell death caused by activation, which allows them to live longer and better fight volume.

Q: Which question did you investigate?

This study was a follow-up of our previously published studies, where we found that INFG was necessary for Car-T cells to kill solid tumor cells, but not blood cancer.

IFNG is a cytokin released by Car-T cells (and normal T cells) when activated that cause inflammation. If it is released too much IFNG, it can cause toxicities in patients. Therefore, we created Car-T cells that did not release ifng.

In blood cancers, this led to reduced inflammation without affecting how well the CAR-T cells kill the tumor. However, in solid tumors, CAR-T cells that did not release IFNG did not kill tumor cells.

In both cases, CAR-T cells that do not release ifng tend to extend more and live more or more, two-lear characteristics that would be beneficial to the effectiveness of Car-T cells.

In this study, we have created Car-T cells that still release ifng (to maintain their ability to kill compact tumors), but continue to expand longer and live longer, as if they did not release Ifng.

Q: What methods or approach did you use?

We used CRISPR/CAS9 to hit the expression of the IFNG receptor (Ifngr) in Car-T cells. Without this receptor, IFNG has no signaling in the Car-T cell.

We used T cells from healthy donors to make Car-T Car-T-Knockout IFNGR cells and examine their function in response to cancer cell rows on a plate.

We also injected these Car-T cells in tumors mice to prove their improved persistence and function in a preclinical model.

Q: What did you find?

We found that IFNGR’s blow to Car-T cells enhanced the extension, perseverance and anti-ango of the activity in both dishes and mice, enhancing their effectiveness and durability.

CAR-T cells that were unable to respond to IFNG signaling were subjected to less cell death after activation-ie deleting IFNGR that prevents CAR-T cells from the pause.

Overall, this has led to an increase in the effectiveness and extension of Car-T cells to multiple models of compact tumors.

Q: What are the consequences?

These findings indicate that the IFNGR strike of Car-T cells will improve their effectiveness to target any type of tumor by extending their survival and allowing them to kill more cancer cells.

Q: What are the next steps?

We hope to start a clinical trial of these Car-T cells in compact tumors, either in collaboration with a company or as a spin-out attempt.

Writing: In addition to Maus, Bailey, Takei and Escobar, other authors from mass general Brigham include Michael C. Kann, Amanda A. Bouffard, Tamina Kienka, Valentina M. Super, Alexander Armstrong, Diego Salas-Benito, Merle K. Phillips, Filippo Birocchi, Sonika, Harrison, Irene Sanfò Grauwet, Eli P. Darnell, Charlotte E. Graham, Mark B. Leick, Felix Korell and Trisha R. Berger.

Source:

Magazine report:

Bailey, Sr, et al. (2025). IFN-c CD28 CAR cells show increased survival, efficiency and resistance to multiple mouse volume models. The translation medicine of science. doi.org/10.1126/scitranslmed.adp8166.

cell cells Improve solid strengthening survival Treatment tumor
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