Recently, fromHengrui YuanzhengThe R&D team inNature CommunicationsPublished in the journal (Impact Factor 16.6) titledHLA-class II restricted TCR targeting human papillomavirus type 18 E7 induces solid tumor remission in miceThe research paper provides a detailed introduction to the development process, mechanism of action, and preclinical efficacy and toxicology studies of HRYZ-T101, the company's first TCR-T product to enter the clinical stage.HRYZ-T101 is a global first-in-class innovative drug, featuring a new target, new structure, and new mechanism, and it has not been marketed in or outside of China.。
Cervical Cancer is one of the most common malignant tumors in gynecology, ranking fourth in the incidence of female malignant tumors. Currently, there is no recommended treatment plan for metastatic or recurrent cervical cancer patients who have failed second-line chemotherapy both in China and internationally. Studies have confirmed that over 95% of cervical cancer cases are associated with...HPV(HPV) related, with types 16 and 18 being the most common. In addition, HPV infection can also lead to various head and neck cancers and anogenital tumors. Tumor cells that undergo carcinogenesis after HPV infection will continuously overexpress the E7 viral protein, which is not expressed in normal tissues and serves as an excellent target for targeted therapies such as TCR-T.
In this study, the research teamBased on TCR Reverse Genetic Engineering（Reverse Genetic Engineering of TCR，ReGET) Platform Technology, successfully cloned from a patient who benefited from early multi-antigen autologous immune cell therapy (MASCT)Targeting HPV18 E7 Tumor AntigenThe TCR molecule (10F04 TCR). The patient was diagnosed with HPV-positive advanced metastatic squamous cell carcinoma of the cervix in 2011 and relapsed after conventional treatments such as surgery, chemotherapy, and radiotherapy. After receiving multiple courses of MASCT treatment starting from 2014, the patient's tumor gradually regressed and achieved long-term remission, which has lasted to date.Tumor-free survival for more than nine yearsThe long-term presence of specific T cells targeting multiple tumor antigens such as HPV18 E7 in the patient's body is a possible reason for the patient's clinical benefit.▲Overview of MASCT Immunotherapy Benefits and Immune Response The research results confirmed that the 10F04 TCR specifically recognizes the HPV18 E7 antigen peptide presented by the high-frequency HLA-II molecule HLA-DRB1*09:01 in the Chinese population, demonstrating strong anti-tumor activity both in vitro and in mouse models. The results showed,10F04 TCR can simultaneously mediate the recognition and direct killing of antigen-positive tumor cells in both CD4+ and CD8+ T cells, and release IFNγ.TNFα, IL2, Granzyme B and other anti-tumor cytokines, further inducing tumor cell apoptosis and promoting the expansion of TCR-T cellsAt the same time, the IFNγ cytokines secreted by the activated TCR-T cells can also induce the upregulation of HLA molecule expression on the tumor surface, making them more sensitive to TCR-T recognition.In recent years, an increasing number of clinical research results have shown that CD4+ tumor-recognizing T cells play a crucial role in tumor treatment by directly killing tumor cells, assisting CD8+ T cells in their cytotoxic effects and long-term persistence, and secreting cytokines to activate dendritic cells (DCs), macrophages, and other components of the innate immune system to achieve anti-tumor effects. This study reports on the 10F04 TCR molecule.Can simultaneously activate CD4+ and CD8+ T cells and secrete multiple cytokines.; At the same time, this study also conducted cross-recognition validation of the human proteome and major HLA molecules, and no off-target risk was found for 10F04TCR.▲10F04 Preclinical Efficacy of TCR-T Cells
Currently, the HRYZ-T101 product has received CDE approval for the treatment of HPV18-positive solid tumors, and the first patient has completed infusion in the Phase I registrational clinical trial.
● About Hengrui Yuanzheng
Hengrui Yuanzheng Biotechnology Co., Ltd. is a biopharmaceutical company focusing on cell and gene therapy (CGT), jointly established in 2015 by Jiangsu Hengrui Pharmaceutical Group and Shenzhen Yuanzheng Cell Medical Technology Co., Ltd. The company is dedicated to the immunotherapy of solid tumors and has developed multiple product pipelines based on tumor-specific T-cell receptors (TCR) and multi-target autologous immune cells (MASCT). Among them,MASCT-I is the world's first dual immunocyte therapy product to receive IND approval and has entered Phase II clinical trials.; HRYZ-T101, the first TCR-T product incubated through the company's independently developed ReGET platform, has also received IND approval and entered Phase I clinical stage.The ReGET platform can continuously incubateTCR Molecule with Global Originality Based on HLA Typing in Asian Populations, solving the "bottleneck" issue of TCR products always being based on HLA typing of European and American populations. The company's latest TCR fusion protein product further addresses the "off-the-shelf" challenge in cell therapy, significantly improving drug accessibility and potentially benefiting more Chinese patients with solid tumors. The company holds over 60 core patents in its main business and has been granted authorization in multiple countries and regions, including China, the United States, the European Union, and Japan.
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Disclaimer: The content is sourced from Hengrui Yuanzheng, Songhe Capital, and other sources. This article aims for knowledge sharing. All content is for reference only and does not constitute any advice.。
