Leticia Tordesillas, PhD, on the Potential of γδ CAR T-cells to Treat Bone Metastatic Prostate Cancer

“It's important to have more information about γδ T-cells as a platform for the CAR because right now they are emerging now as an alternative to αβ T-cells. So, with this study that we have done looking at the kinetics—and how zoledronate can impact the kinetics of the γδCAR T-cells in vivo—I think that we will have more information...”

Following the success seen in treating hematological malignancies with chimeric antigen receptor T-cell (CAR-T) therapies, many researchers are now evaluating the potential of developing CAR-T treatments for solid tumors. In order to overcome the challenges presented by the solid tumor microenvironment, some investigators are studying γδ CAR T-cells as an alternative to αβ CAR T-cells for the basis of new therapies. In addition, some are also exploring the potential of combination therapies that use CAR-T in conjunction with traditional drugs.

Leticia Tordesillas, PhD, a research scientist at Moffitt Cancer Center, presented a poster entitled, “Biodistribution of zoledronate and effects on gd PSCA-CAR T cells in a model of bone metastatic prostate cancer,” at the American Association for Cancer Research (AACR) Annual Meeting 2023, held April 14-19, 2023, in Orlando, Florida. The poster details the results of mouse model research evaluating γδ CAR T-cells in combination with zoledronate (ZOL) for the treatment of bone metastatic prostate cancer.

In an interview with CGTLive™’s sister publication, OncLive®, Tordesillas discussed the methods used in the study and gave an overview of the key results. Tumor cells were injected into the tibias of mice to model bone metastasis. Some of the mice were then treated with ZOL while others did not receive ZOL; afterwards, all of the mice received treatment with γδ CAR T-cells targeted at prostate stem cell antigen (PSCA). The investigators observed greater anti-tumor effect in the mice who received both ZOL and γδ PSCA-CAR T-cells in comparison to the mice who received γδ PSCA-CAR T-cells alone. The study also examined the kinetics and biodistribution of the treatment. In addition to discussing the results of the study, Tordesillas also touched on how the findings might inform future combination approaches in oncology and spoke about areas of interest for future study, specifically mentioning the need to look more closely at the biology of the interactions between the different components in the tumor microenvironment.

Click here to read more coverage of the AACR 2023 Annual Meeting.

REFERENCE
Tordesillas L, Cianne J, Frieling JS, Bustos X, Lynch CC, Abate-Daga D. Biodistribution of zoledronate and effects on gd PSCA-CAR T cells in a model of bone metastatic prostate cancer. Presented at: American Association for Cancer Research Annual Meeting. April 14-19, 2023; in Orlando, Florida. Abstract 1767/1