Graft-Versus-Host Disease (GVHD) Toxicity in CAR-T Therapy

GVHD (Graft-Versus-Host Disease) is a condition that typically occurs after allogeneic stem cell transplantation, where the donor’s immune cells attack the recipient’s tissues. While CAR-T therapy does not inherently involve stem cell transplantation, GVHD can still occur in specific cases—particularly when using CAR-T cells derived from a donor (allogeneic CAR-T therapy).

Why Does GVHD Happen in CAR-T Therapy?

GVHD occurs in allogeneic CAR-T therapy, where T cells from a donor (rather than the patient’s own cells) are genetically modified and infused into the patient. Since these T cells come from another individual, they may recognize the recipient’s tissues as "foreign" and start attacking them, leading to GVHD.

Types of GVHD in CAR-T Therapy

Acute GVHD (aGVHD): Develops within the first few weeks or months after treatment, typically affecting the skin, liver, and gastrointestinal tract (causing rash, jaundice, or severe diarrhea).

Chronic GVHD (cGVHD): Occurs later, leading to fibrosis and long-term immune complications, affecting multiple organs.

How Common is GVHD in CAR-T Therapy?

  • Autologous CAR-T therapy (where the patient’s own cells are used) does NOT cause GVHD, since the cells are already recognized as "self."
  • Allogeneic CAR-T therapy (donor-derived CAR-T cells) has a risk of GVHD, though researchers are developing strategies to reduce it.

How is GVHD Managed in CAR-T Therapy?

Genetic Editing: CRISPR and other gene-editing tools are being explored to remove T-cell receptors (TCR) from allogeneic CAR-T cells to prevent GVHD.
Immunosuppressive Drugs: If GVHD occurs, drugs like steroids, cyclosporine, or ruxolitinib can help control immune overactivation.
TCR-Deleted CAR-T Cells: Some CAR-T cell therapies use T-cell receptor-depleted donor T cells to minimize GVHD risk.

Future Directions

Researchers are working on universal donor CAR-T cells ("off-the-shelf" CAR-T therapy) that can be used safely in any patient without triggering GVHD, making treatment more accessible and efficient.
In summary, GVHD is primarily a concern in donor-derived (allogeneic) CAR-T therapy, but ongoing advances are helping to mitigate this risk, making CAR-T treatment even safer and more effective.

Sources:

  1. Graft-versus-host disease risk after chimeric antigen receptor T-cell therapy ( pubmed.ncbi.nlm.nih.gov)
  2. Extracorporeal photopheresis as a promising strategy for the management of graft-versus-host disease after CAR T-cell therapy (ashpublications.org)
  3. Allogeneic CAR T-Cell Therapy Potentially Reduces GVHD Risk (targetedonc.com)
  4. Graft-Versus-Host Disease after Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Post Allogeneic Hematopoietic Cell Transplantation: (ashpublications.org)

Publication: March 2025