| Autor: |
Stephen J. Bagley, Zev A. Binder, Arati S. Desai, Maclean P. Nasrallah, Eileen Maloney, Steven Brem, Robert Lustig, Goldie Kurtz, Michelle Alonso-Basanta, Suyash Mohan, Wei-Ting Hwang, Oliver Y. Tang, Meghan Logun, Meghna Bhattacharyya, Kelly Markowitz, Devora Delman, Amy Marshall, Cecile Alanio, Gregory L. Beatty, Jennifer L. Brogdon, Elizabeth Hexner, Donald M. O'Rourke |
| Rok vydání: |
2023 |
| Popis: |
Treatment efficacy with chimeric antigen receptor (CAR) T cell therapy in glioblastoma (GBM) is undermined by an immunosuppressive tumor microenvironment (TME). We previously showed that CAR T cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces anti-tumor activity against recurrent GBM and causes upregulation of programmed death-ligand 1 (PD-L1) in the TME. Here, we conducted a phase I trial to study the impact of CART-EGFRvIII cells administered concomitantly with the PD-1 inhibitor pembrolizumab in patients (n = 7) with newly diagnosed, EGFRvIII + GBM. Treatment was well tolerated without incidence of dose-limiting toxicity. However, no signal of efficacy was detected with a median progression-free survival of 5.2 months (90% CI, 2.9–6.0 months) and median overall survival of 11.8 months (90% CI, 9.2–14.2 months). In addition, PD-1 expression in the CART-EGFRvIII infusion product did not correlate with outcomes, and peripheral CAR T cell engraftment was relatively short-lived. Together, these findings show the safety of combining CAR T cells and PD-1 inhibition in GBM but given the lack of efficacy, also indicate a need to consider alternative combinatorial strategies. ClinicalTrials.gov registration: NCT03726515. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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