AvenCell Doses First Patient with World's First CRISPR-Engineered Dual-Targeting Allogeneic CAR-T Therapy
核心洞察
AvenCell Therapeutics (搜索) has dosed the first patient in its Phase I QUADvance study with AVC-203, marking the world's first CRISPR-engineered allogeneic CAR-T therapy to simultaneously target CD19 (搜索) and CD20 (搜索) antigens.
The therapy incorporates four key innovations including dual antigen targeting, immune evasion through CRISPR engineering, improved T-cell fitness from healthy donors, and switchable targeting capabilities for future indication expansion.
The program is supported by a $40 million grant from Japan's AMED and received FDA IND clearance and EMA approval on first submission, enabling trial initiation across multiple sites in the US and Europe.
AvenCell Therapeutics (搜索) has achieved a significant milestone in allogeneic cell therapy by dosing the first patient with AVC-203, the world's first CRISPR-engineered allogeneic CAR-T therapy designed to simultaneously target CD19 (搜索) and CD20 (搜索) antigens. The Phase I QUADvance study (AVC-203-01; NCT07284433) represents a breakthrough approach for treating relapsed/refractory B-cell malignancies (搜索).
Revolutionary Dual-Targeting Technology
AVC-203 is engineered to simultaneously target and eliminate cells expressing CD19 (搜索) and/or CD20 (搜索) receptors, which are expressed in nearly all B-cell malignancies (搜索), including diffuse large B-cell lymphoma (搜索) (DLBCL). The therapy incorporates a novel, dimerized receptor construct that combines constitutive CD19/CD20 dual-targeting with AvenCell's proprietary RevCAR switchable receptor, enabling future indication flexibility and target expansion beyond CD19/CD20 through bi- or tri-specific bridging proteins.
"Patients with relapsed/refractory B-cell malignancies (搜索) who have exhausted currently available treatment options, including approved autologous CAR-T therapies, have limited alternatives and a poor prognosis," said Professor Martin Wermke, Head of the Early Clinical Trial Unit at the National Cancer Center Dresden (搜索), Germany. "AvenCell's allogeneic approach, combined with its innovative dual-targeting and switchable technology, represents a promising new therapeutic strategy for these patients."
Four Key Innovations
AVC-203 incorporates four distinct technological advances that differentiate it from existing CAR-T therapies:
Dual antigen targeting: AVC-203 CAR-T cells express a proprietary receptor that simultaneously targets CD19 (搜索) and CD20 (搜索), potentially reducing the risk of antigen escape that can limit single-target therapies.
Immune evasion: AvenCell implements a unique, differentiated, and proprietary sequence of CRISPR/Cas9 engineering to enable the use of healthy donor cells versus the patient's own cells, avoiding both Graft-versus-Host Disease (GvHD) and rejection by the patient's immune system.
Improved T-cell fitness and off-the-shelf availability: A proprietary manufacturing process leverages the highly consistent T-cell fitness of healthy donors to eliminate the cost, variability, and complexity of patient-specific production, enabling immediate, massively-scalable treatment.
Switchable targeting: A RevCAR receptor dimerized to the CD19 (搜索)/CD20 (搜索) CAR enables flexible targeting of additional tumor antigens through bi- or tri-specific bridging proteins, allowing future target expansion beyond CD19/CD20.
Addressing Critical Unmet Medical Needs
B-cell malignancies (搜索), including non-Hodgkin lymphomas (搜索), multiple myeloma (搜索), and B-cell acute lymphoblastic leukemia (搜索) (B-ALL), account for the majority of blood cancers. Approximately 120,000 and 150,000 new cases are diagnosed annually in the United States and Europe, respectively. While approved autologous CAR-T therapies have demonstrated meaningful clinical activity in certain B-cell malignancies, significant challenges remain, including lengthy manufacturing timelines, high costs, and limited accessibility.
"Dosing the first patient with AVC-203 is a significant milestone for AvenCell and for the field of allogeneic cell therapy," said Andrew Schiermeier, AvenCell's President & CEO. "We are excited to build on the promising safety and activity observed in our ongoing allogeneic CAR-T clinical program in AML (AVC-201-01) by now entering B-cell lymphoma with what we believe to be the most scientifically compelling allogeneic technology in the industry."
Global Support and Regulatory Approval
The AVC-203 program has garnered significant international support, receiving a grant of up to $40 million from the Japan Agency for Medical Research and Development (AMED) under the "Strengthening Program for Pharmaceutical Startup Ecosystem." The grant will support the advancement of AVC-203 toward clinical development in Japan, with the goal of bringing this innovative therapy to patients across the Asia-Pacific region.
AvenCell received both FDA IND clearance and EMA approval of its Clinical Trial Application (CTA) for the QUADvance study on first submission in late 2025, enabling trial initiation at multiple sites in the US and Europe. The QUADvance study is a Phase I/II trial evaluating the safety, tolerability, efficacy, and pharmacokinetics of AVC-203 in adults with relapsed or refractory B-cell malignancies (搜索), with planned expansion to Japan.
Transformative Manufacturing Approach
AvenCell's allogeneic approach aims to address the limitations of current autologous CAR-T therapies through off-the-shelf availability, consistent product quality, and scalable manufacturing. The company's goal is to ensure that any patient who can benefit from CAR-T therapy can receive it through massive scaling of supply and dramatic reductions in cost of goods.
The company, founded in 2021 by Blackstone Life Sciences (搜索), Cellex Cell Professionals (搜索), and Intellia Therapeutics, is headquartered in Watertown, Massachusetts, with research, clinical and manufacturing operations in Dresden, Germany. AvenCell incorporated the clinical-stage biopharmaceutical company GEMoaB GmbH and is building a transformative cell therapy platform targeting difficult-to-treat cancers, with lead programs focusing on acute myeloid leukemia (搜索) (AML) and B-cell malignancies (搜索), and additional programs targeting other hematological malignancies, auto-immune diseases, and solid tumors.