Anti-glioma CAR-T targets have heterogenous expression and distinct tumor coverage among glioma subtypes, and closely correlate with glioma malignant or immune phenotypes.

Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.

P1, N=10, Recruiting, Beijing Tiantan Hospital | Not yet recruiting --> Recruiting

These data provide an approach for achieving both intracellular inhibitory molecule, SHP-1 deletion and CD133 CAR gene over-expression in human T cells. And SHP-1 could be a new potential target for adoptive CAR T cells immunotherapy.

In summary, these data suggest that CD133 plays a critical role in fueling the growth of BM, and immunotherapeutic targeting of this cell population is a feasible strategy to control the outgrowth of BM tumors that are otherwise limited to palliative care.

Our study provides a nonviral strategy for constructing CAR-T cells that could also secrete checkpoint blockade inhibitors based on a Sleeping Beauty system from minicircle vectors and revealed a potential benefit of this strategy for male patients with advanced HCC and high CD133 expression (median immunohistochemistry score > 2.284).

More importantly, we demonstrated a rationale and efficacy to combine the novel CAR-T and anti-PD-1 with radiotherapy in solid tumor, which was a paradigm-shifting finding and was implicational for future clinical use. Our study was fully fleshed out and ready to be published.

However, in long-term coculture and after tumor re-challenge, 133CARTsL showed lower expression of programmed cell death protein (PD-1) and better cytotoxic function against high CD133 and PD-L1 CCA cells. The higher potential of 133CARTsL with reduced exhaustion profile would offer great promise for application of CD133-targeting CAR T cells in solid tumors.

We show GPNMB influences tumor-intrinsic biology of GBM and is also active in macrophages in the recurrent GBM immune microenvironment. By targeting GPNMB along with CD133, combinatorial therapeutic regimens could target both the cancer stem cell hierarchy and its supportive niche. Administration of both CAR-T cell therapies to humanized mice engrafted with patient-derived GBMs will provide better cytotoxic coverage and potentially provide more durable therapeutic efficacy for GBM patients.

P1, N=10, Not yet recruiting, Beijing Tiantan Hospital | Initiation date: Nov 2022 --> May 2023

By targeting GPNMB along with CD133, combinatorial therapeutic regimens could target the cancer stem cell hierarchy and its supportive niche. We therefore plan to administer both CAR-T cells to provide better cytotoxic coverage and increase efficacy.

Our study suggests that it is with higher efficiency and more safety to prepare bispecific CAR T cells through non-viral mcDNA vectors. CoG133-CAR T cells have enhanced tumor-suppression capacity through dual antigen recognition and internal activation. It provides an innovative strategy for CAR T therapy of HCC, even solid tumors.