Leticia Tordesillas, PhD, on Investigating CAR-T Combination Treatment for Bone Metastatic Prostate Cancer

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The research scientist at Moffitt Cancer Center shared the rationale behind the preclinical study she presented at the 2023 AACR annual meeting.

“A specific challenge always with CAR T-cells: You have to find the right antigen to be targeted. In this case, PSCA is highly expressed in prostate tumor cells, specifically those with metastases in bone—so, they have high expression—and the expression of PSCA is low in healthy tissues, so we think that we won't be observing high toxicities related with this CAR.”

Metastatic castrate resistant prostate cancer often migrates to bones. Although the bisphosphonate zoledronate (ZOL) is available for palliative care in clinical practice, great unmet need remains for patients with bone metastatic prostate cancer, which is currently an incurable disease. In response to this, some researchers are investigating the potential of chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of these patients.

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 ZOL for the treatment of bone metastatic prostate cancer.

In an interview with CGTLive™’s sister publication, OncLive®, Tordesillas discussed the rationale behind the study. She spoke about the unmet needs for patients with bone metastatic prostate cancer and emphasized the need to develop new treatments. Tordesillas also discussed the specifics behind why this particular combination method was chosen for evaluation, noting that ZOL is known to induce the accumulation of phosphoantigens in tumor cells, which are recognized by γδ T-cells' endogenous T-cell receptors. In addition, the CAR-T used in this research features a CAR that targets prostate stem cell antigen (PSCA), an antigen highly expressed in prostate tumor cells, but only expressed at low levels in healthy cells.

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
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