Targeting CEA in metastatic triple negative breast cancer with image-guided radiation followed by Fab-mediated chimeric antigen receptor (CAR) T-cell therapy
2024

Combining Radiation Therapy and CAR-T Cells for Breast Cancer Treatment

Sample size: 10 publication 10 minutes Evidence: high

Author Information

Author(s): Aniogo Eric, Kujawski Maciej, Awuah Dennis, Cha Seung E., Espinosa Ruby, Hui Susanta, Ghimire Hemendra, Yazaki Paul J., Brown Christine E., Wang Xiuli, Shively John E.

Primary Institution: City of Hope, Duarte, CA, United States

Hypothesis

Prior treatment with Image-Guided Radiation Therapy (IGRT) would increase CAR-T cell tumor infiltration, leading to improved antigen specific expansion of CAR-T cells.

Conclusion

The combination of IGRT and anti-CEA scFab CAR-T therapy effectively targets both primary tumors and distant metastases in triple-negative breast cancer.

Supporting Evidence

  • The anti-CEA scFab CAR-T cells showed robust in vitro expression and lysis of CEA-positive TNBC cells.
  • Significantly higher IFN-γ production was observed in CD28z-CAR-T cells compared to 4-1BBz-CAR-T cells.
  • Combined IGRT and CAR-T therapy resulted in significant tumor growth reduction compared to either therapy alone.

Takeaway

This study shows that using radiation therapy before CAR-T cell treatment helps the CAR-T cells work better against breast cancer.

Methodology

The study involved engineering anti-CEA CAR-T cells and testing their efficacy in vitro and in vivo using a metastatic triple negative breast cancer model.

Limitations

The study was limited to CAR-T therapy in immunocompromised animals, restricting the ability to assess potential toxicity.

Participant Demographics

The study used T cells from healthy human donors.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.01

Digital Object Identifier (DOI)

10.3389/fimmu.2024.1499471

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication