On September 4, Shenzhen Cell Valley Biopharmaceutical Co., Ltd., in collaboration with The First Hospital of Jilin University, the University of California, Irvine, and other domestic and international research institutions, published original research online in the top international life sciences journal Cell Research (5-year average impact factor 35) titled "CD55 organizes lipid raft-LCK signaling to potentiate NK-cell antitumor immunity" .

This study breaks through the long-held traditional view of CD55 primarily as a "complement regulatory protein" and, for the first time, systematically reveals its critical mechanistic role in NK cell antitumor immunity . The research further demonstrates that continuously enhancing CD55 expression in NK cells through engineering approaches can significantly improve the antitumor activity, in vivo persistence, and therapeutic efficacy of CAR-NK cells, providing a new molecular target and engineering pathway for the development of next-generation, highly effective CAR-NK cell drugs.

Multi-Institutional Collaboration Drives Deep Integration of NK Cell Basic Mechanisms and Engineering Translation

This study was completed in collaboration with The First Hospital of Jilin University, the School of Basic Medicine at Jilin University, Jilin University's international collaborative research platforms in future science, the School of Medicine and Chao Family Comprehensive Cancer Center at the University of California, Irvine, and Shenzhen Cell Valley Biopharmaceutical Co., Ltd.

This collaboration fully leveraged the respective strengths of universities, clinical medical centers, international oncology research teams, and cell therapy industrialization platforms, forming a complete research chain spanning fundamental tumor immunology mechanism research, single-cell omics analysis, genetic engineering, CAR-NK construction, and in vivo therapeutic validation .

Core Breakthrough: Discovery of a Previously Unknown Autonomous Activation Signaling Pathway in NK Cells

NK cells are a critical component of the body's natural antitumor immune system and are the core effector cells for novel cell therapy technologies such as CAR-NK. However, a long-standing clinical translation challenge is that NK cells often rapidly lose function or become "exhausted" upon entering the tumor microenvironment (TME), significantly limiting their killing capacity and in vivo persistence .

Through RNA sequencing, mass cytometry, single-cell sequencing, gene editing, molecular interaction studies, and multiple in vitro and in vivo tumor models, the research team discovered that:

CD55 is not merely a complement regulatory molecule but an important "membrane signaling organizer" for NK cells .

When NK cells first encounter tumor cells, tumor recognition activates the NKG2D–PI3K/AKT–p65 signaling pathway, rapidly inducing NK cells to upregulate CD55. Subsequently, CD55 on the NK cell surface interacts in trans with CD97 on the tumor cell surface, further driving the aggregation of lipid rafts on the cell membrane and recruiting and activating LCK kinase, ultimately promoting NK cell killing, cytokine release, and proliferation .

Thus, this study proposes and validates a complete:

CD97 → CD55 → lipid raft aggregation → LCK activation NK cell antitumor signaling axis .

From Mechanism Discovery to Engineering: CD55 Poised to Become a "Booster Module" for Next-Generation CAR-NK

What is even more translationally valuable is that the team not only discovered this mechanism but also further validated it through engineering approaches and has already filed relevant invention patents.

The researchers constructed NK cells with sustained CD55 expression and found that under conditions of prolonged tumor stimulation, CD55-engineered NK cells maintained stronger and more durable tumor-killing capacity .

Building on this, the team further constructed engineered CAR-NK cells co-expressing CD19 CAR and CD55 (CD19CAR-CD55 NK). Animal experiments demonstrated that compared with conventional CD19 CAR-NK, CD55-enhanced CAR-NK exhibited:

Higher LCK signaling activity、Stronger tumor-killing capacity、Higher levels of CD107a and IFN-γ、Better in vivo expansion and persistence、Significantly improved tumor control efficacy .

Cell Valley Continues to Advance NK/CAR-NK Innovative Technologies Toward Clinical Translation

As a collaborating institution in this study, Shenzhen Cell Valley has long focused on the R&D and clinical translation of cell and gene therapy technologies, continuously building technical capabilities in process development, genetic engineering, large-scale manufacturing, and quality control of NK and CAR-NK cell products.

This study, starting from fundamental immune mechanisms, further completed CAR-NK engineering and in vivo therapeutic validation, providing important scientific evidence for subsequent process optimization, indication expansion, and preclinical translational research of CD55-enhanced NK/CAR-NK products.

Going forward, Cell Valley will continue to collaborate with domestic and international universities, hospitals, and research institutions to promote the deep integration of basic research, engineering technologies, and clinical needs, accelerating the translation of next-generation NK and CAR-NK technologies with independent innovation value toward clinical applications, and providing more innovative cell therapy options for cancer patients.

Paper Information

Title: CD55 organizes lipid raft-LCK signaling to potentiate NK-cell antitumor immunity

Journal: Cell Research

Online Publication Date: September 4, 2026

DOI: 10.1038/s41422-026-01288-8