▎Report by the WuXi AppTec Content Team

According toAccording to publicly available information from Tsinghui Lianuo,QH104 is a B7H3-targeted allogeneic universal CAR-γδ T cell therapy developed by the company. This product utilizes a unique γδ T cell engineering strategy, capable of simultaneously recognizing tumor surface antigens and specific metabolites, demonstrating promising therapeutic effects against various tumors in preclinical studies. Additionally, this product is an off-the-shelf universal cell therapy, significantly reducing production costs compared to autologous cell therapies, with good clinical accessibility.

To be presented at the ESMO conference is the first-in-human clinical trial of QH104. The primary objective of this study is to evaluate the safety and tolerability of intrathecal infusion of QH104 in treating B7H3-positive rGBM, with secondary objectives being to assess the pharmacokinetic characteristics and preliminary efficacy of the reinfused cells. Participants received intrathecal injections of QH104., the dose was escalated according to the "3+3" method (1/3/10×10⁷CAR+ cells), administered once a month。

As of March 30, 2024, a total of 7 patients (2 female, 5 male, median age 60 years, age range 31-66 years) with high-grade rGBM have received more than one intrathecal infusion of QH104. The median observation time was 6.5 months, with a range of 3 to 10 months. Subjects tolerated the treatment well, with no dose-limiting toxicity (DLT). The most common adverse events were fever and headache, accompanied by elevated levels of IL-6 and IFN-γ in the cerebrospinal fluid; no grade 3 or higher severe adverse events occurred.Cytokine Release Syndrome (CRS)Or ICANS, was not observed eitherGraft-versus-Host Disease (GvHD)。

Efficacy data show that the objective response rate (ORR) was 42.9% in 7 patients., Disease Control Rate (DCR) was 100%QH104 also demonstrated good persistence.Thirty days after administration, the injected cells could still be detected by flow cytometry and qPCR.. Preliminary stratified analysis found that clinical efficacy was positively correlated with the expression level of B7H3.Researchers believe that QH104 has good safety and shows promising clinical potential for treating B7H3-positive rGBM patients.

Public information shows that TsingHui Union Biotech was established in 2018,Founded by Professor Yonghui Zhang from the School of Pharmaceutical Sciences at Tsinghua University,Focus on the development of γδ T cell innovative drugs in the fields of oncology, infectious diseases, and communicable diseases.

γδ T cells are a special subset of T cells expressing γδ TCR, which combine adaptive and innate immune functions and can specifically recognize and eliminate tumor cells.Unlike αβ T cells that recognize MHC peptide complexes, γδ T cells recognize by binding to butyrophilins (BTN family proteins).Within tumor cellsThe accumulated lipid metabolism intermediates IPP/DMAPP (phosphoantigens) enable γδ T cells to be used in allogeneic settings without causing graft-versus-host disease (GvHD). The clinical translational potential of such products is worth further investigation.

References:

[1]ESMO Conference Official Website. fromhttps://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/19

[2] QH104 Clinical Trial Results by Qinghui Lianuo to Debut at 2024 ESMO Congress. Retrieved July 19， 2024, from  https://mp.weixin.qq.com/s/NcCdqBz1d-FVc6hgUOUy2Q