Shenzhen Cell Valley joins forces with the team of Academician Yan Xi Yun and Lu Daopei Hospital to pioneer a new clinical breakthrough in dual-target CAR-T therapy for AML— the world's first CLL1-CD146 CAR-T project approved by the Ethics Committee, bringing new hope to patients with relapsed/refractory AML.

Recently, the "Clinical Study on the Safety and Efficacy of CLL1-CD146 CAR-T Cell Product in Treating Relapsed/Refractory Acute Myeloid Leukemia (AML)", jointly conducted by Shenzhen Cell Valley Biopharmaceutical Co., Ltd. (hereinafter referred to as "Shenzhen Cell Valley") and Lu Daopei Hospital, was successfully approved by the Ethics Committee. This milestone event marks the official entry of the world's first dual-target CAR-T immunotherapy project for AML into clinical translation, opening a new therapeutic pathway for relapsed/refractory AML patients globally.

Breakthrough Dual-Target Strategy:

Addressing Clinical Challenges in AML Treatment

Acute Myeloid Leukemia (AML) is a highly aggressive hematologic malignancy, particularly for relapsed/refractory (R/R) patients ineligible for transplantation. Traditional chemotherapy or transplantation therapies have limited efficacy, with a 5-year survival rate below 30%, highlighting an urgent unmet clinical need. The newly approved CLL1-CD146 dual-target CAR-T project innovatively adopts the "Niche-Targeting" strategy, simultaneously targeting the CLL1 antigen on AML tumor cells and the CD146 antigen on stromal cells in the tumor microenvironment, achieving dual efficacy in tumor suppression and relapse reduction.

Preclinical studies demonstrate that this dual-target CAR-T cell exhibits significantly superior in vitro killing efficiency, anti-exhaustion capability, and in vivo anti-tumor activity compared to single-target CAR-T. Notably, in simulated tumor relapse experiments with three rounds of stimulation, it showed lower expression levels of exhaustion markers such as PD-1 and LAG3, highlighting its long-term anti-tumor potential and providing robust scientific evidence for clinical efficacy.

This clinical study, conducted in collaboration with Professor Lu Peihua, Executive President of Lu Daopei Hospital, employs an open-label, single-arm, dose-escalation design. It plans to enroll 20 relapsed/refractory AML patients aged 14-65, divided into low, medium, and high dose groups to gradually explore the optimal therapeutic dose, with a study duration of 24 months.

The study will focus on uating the safety (e.g., adverse reactions such as cytokine release syndrome and neurotoxicity) and efficacy (including key metrics like complete response rate, overall survival, and progression-free survival) of CAR-T cells, while also exploring the impact of cellular kinetic characteristics and CD146 expression levels on therapeutic outcomes to provide a basis for personalized treatment plans.

The project process strictly adheres to regulatory requirements, implementing GMP-level management and dynamic monitoring throughout all stages—from peripheral blood mononuclear cell (PBMC) collection and CAR-T cell preparation/quality control to lymphodepletion preconditioning, cell reinfusion, and long-term follow-up—ensuring the standardization and safety of the clinical study.

Ethics Approval Milestone:

Embarking on a New Journey in Cell Therapy

The approval by the ethics committee not only signifies high recognition of the project's scientific rigor and ethical compliance but also marks a critical step in advancing dual-target CAR-T technology from basic research to clinical application. It is reported that this project will provide a novel treatment option for relapsed/refractory AML patients, particularly those unresponsive to conventional therapies, offering the potential for disease remission or even cure through precision-targeted immune cell therapy.

CD146 is expressed on stromal cells that constitute the AML niche, especially mesenchymal stem cells (MSCs), and recent studies indicate its involvement in promoting the proliferation and survival of malignant myeloid cells. Targeting CD146 represents a highly valuable strategy for addressing the AML niche. As an auxiliary target, CD146 helps overcome the AML tumor microenvironment, enhances the anti-tumor efficacy of CLL1 CAR-T, and reduces relapse rates! This study is a world-first initiative with significant clinical translation and application prospects. The team led by Academician Yan Xiyun from the Chinese Academy of Sciences discovered CD146 as a tumor vascular marker molecule. The CLL1-CD146 dual-target CAR-T cells in this study were jointly developed by Academician Yan Xiyun's team and the Shenzhen Cell Valley team.

Shenzhen Cell Valley:

Empowering Clinical Translation with Cutting-Edge Capabilities

As a core project partner, Shenzhen Cell Valley is the only CRO/CDMO enterprise in China with clinical-grade retroviral vector GMP industrial production capabilities, and its full-industry-chain strength provides critical support for project implementation. Shenzhen Cell Valley boasts over 10,000 square meters of GMP cleanrooms and R&D laboratories, certified by the ISO9001 quality management system and registered as a P2 laboratory. It has established a comprehensive system covering viral vector packaging, full-process cell production, and quality control, achieving a 100% success rate in clinical-grade cell product preparation. With large-scale production capabilities, over a thousand standardized operating procedures (SOPs) ensure production consistency, and its viral vectors and cell products have received dual recognition from China's CDE and the U.S. FDA. Clinically, it has provided IIT ethical documentation support and established substantive collaborations with over 100 top-tier hospitals, with more than 20 cell therapy projects approved by ethics committees. Collaborations span various fields, including hematologic malignancies and autoimmune diseases, with long-proven technology translation capabilities.

Professor Shi Yuan Yuan, Chairman of Shenzhen Cell Valley, stated: "This collaboration exemplifies the deep integration of cell therapy technology with clinical needs. Leveraging our core strengths in viral vector production and cell preparation, we will work hand in hand with Hebei Yanda Lu Daopei Hospital to advance research progress, striving to bring groundbreaking therapies to patients as soon as possible and propel China's cell therapy technology to the global forefront."

In the future, as this clinical study progresses, the CLL1-CD146 CAR-T technology is expected to become the 'next-generation benchmark' for AML treatment, contributing Chinese wisdom and solutions to the global field of hematologic malignancy therapy.