P1, N=36, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P1, N=21, Recruiting, Marcela V. Maus, M.D.,Ph.D. | Trial completion date: Jan 2027 --> Jun 2027 | Trial primary completion date: Jan 2026 --> Jun 2026

Extracellular vesicles (EVs), secreted under hypoxia, can deliver modified bioactive cargo that reprograms recipient cells...These findings show that hypoxia-driven EVs can propagate pro-metastatic signalling in less aggressive and normal prostate cells. The findings highlight EVs as a potential therapeutic target in PCa progression.

P1, N=21, Recruiting, Marcela V. Maus, M.D.,Ph.D. | Trial completion date: Jun 2026 --> Jan 2027 | Trial primary completion date: Jun 2025 --> Jan 2026

P1, N=50, Enrolling by invitation, Shanghai Simnova Biotechnology Co.,Ltd.

Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants. (Funded by Gateway for Cancer Research and others; INCIPIENT ClinicalTrials.gov number, NCT05660369.).

P1, N=16, Recruiting, Shanghai Simnova Biotechnology Co.,Ltd. | Trial primary completion date: Aug 2023 --> May 2024

In exploratory analyses, comparison of the TME in tumors harvested before versus after CAR + aPD1 administration demonstrated substantial evolution of the infiltrating myeloid and T cells, with more exhausted, regulatory, and interferon (IFN)-stimulated T cells at relapse. Our study suggests that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicates a need to consider alternative strategies.

Furthermore, armoring anti-CD19 CAR T cells with SGRP resulted in superior efficacy in a peripheral lymphoma mouse model compared to anti-CD19 CAR T treatment alone, most problably due to innate immune activation. Thus, local anti-EGFRvIII-SGRP CAR T cell therapy combines the potent antitumor effect of engineered T cells with the modulation of the surrounding innate iTME, inducing a synergistic clearance of GBM in a manner that overcomes known mechanisms of CAR T therapy evasion, such as tumor immune suppression and antigen escape.

Here, we conducted a phase I trial to study the safety and tolerability of CART-EGFRvIII cells administered concomitantly with the PD-1 inhibitor pembrolizumab in patients with newly diagnosed, EGFRvIII+ GBM (n=7). Together, these findings suggest that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicate a need to consider alternative immunotherapeutic strategies. ClinicalTrials.gov registration: NCT03726515.

Here, we conducted a phase I trial to study the safety and tolerability of CART-EGFRvIII cells administered concomitantly with the PD-1 inhibitor pembrolizumab in patients with newly diagnosed, EGFRvIII+ GBM (n=7). Together, these findings suggest that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicate a need to consider alternative immunotherapeutic strategies. ClinicalTrials.gov registration: NCT03726515.

As the extension of the approach, we crossed the EGFRvIII-CAR Tg mice with mice carrying Vav-Cre, which allowed the expression of anti-EGFRvIII CAR in all hematopoietic cells...This transgenic mouse model offers rigorous and reproducible evaluations of CAR-expressing hematopoietic cells. Furthermore, the model provides a platform for developing combination therapies, such as CAR-T plus CAR-NKT or CAR-T plus CAR-NK cells, with potential implications for enhanced cancer treatment strategies.