Independently Integrating RVV Gene Delivery and eVLP Editing Delivery to Provide Technical Support for Next-Generation CAR-NK Product Development        

        On October 1, 2026, research achievements independently completed by Shenzhen Cell Valley Biopharmaceutical Group Co., Ltd. were officially published in the internationally renowned immunology journal Frontiers in Immunology (IF 7, Q1). The study focused on CD19/BCMA dual-target CAR-NK cells, integrating retroviral vector (RVV) gene delivery, membrane-bound IL-15 functional enhancement, and engineered virus-like particle (eVLP) editing delivery, validating an internationally pioneering technical route for enhancing the antitumor activity of engineered NK cells.

All authors of the paper are from Shenzhen Cell Valley, with the company as the sole affiliated institution, demonstrating Cell Valley's independent R&D capabilities spanning vector development, cell engineering, and preclinical functional validation.

Combining Dual-Target Recognition with Functional Enhancement to Optimize CAR-NK Product Design

The research team systematically compared tandem and bicistronic CD19/BCMA CAR designs and introduced membrane-bound IL-15. Under the conditions tested in this study, IL-15-armored bicistronic CAR-NK cells exhibited superior in vitro tumor-killing activity compared to the corresponding tandem construct. In a CD19/BCMA double-positive leukemia mouse model, the optimized bicistronic CAR-NK cells effectively reduced tumor burden, delayed disease progression, and significantly prolonged survival, providing a preclinical basis for subsequent product development.

Efficient eVLP Delivery of CREM Editing Successfully Integrated with RVV Gene Delivery

An important innovation of this study was the introduction of eVLP-mediated CREM gene editing into the dual-target CAR-NK manufacturing process: first delivering the editing tool via eVLP, then using RVV to introduce the dual-target CAR and IL-15 expression elements, achieving synergistic application of two delivery technologies.

The study showed that, as estimated by Sanger sequencing and ICE analysis, the insertion/deletion mutation rate at the CREM locus was 94% before CAR transduction and remained 84% after subsequent transduction, validating the feasibility of sequential editing and CAR engineering. After adjusting the proportion of CAR-positive cells in the edited and unedited groups to comparable levels, the CREM-edited group still exhibited significantly stronger overall in vitro tumor-killing activity, providing direct experimental support for this combinatorial engineering strategy.

Leveraging Proprietary Vector Platforms to Continuously Advance Toward Low-Cost, Scaled Manufacturing

This study was built upon Cell Valley's existing BaEV envelope retroviral stable production platform and eVLP platform, further applying foundational delivery capabilities to functionally enhanced CAR-NK products, reflecting the company's synergistic advantages in vector technology and cell product R&D.

From the perspective of industrial translation, the combination of the RVV stable production platform and eVLP editing delivery technology provides a technical foundation for subsequent process standardization, scale-up, and manufacturing cost optimization. Leveraging its independently controlled vector production and cell engineering capabilities, Cell Valley will continue to advance process optimization and translational validation, exploring cell therapy product development pathways that balance antitumor activity, production efficiency, and accessibility.

This research was supported by the Shenzhen Science and Technology Program Peacock Team Project and key industry R&D-related projects.

Paper Information

Title: eVLP-mediated CREM editing enhances cytotoxicity of bicistronic IL-15-armored CD19/BCMA dual-target CAR-NK cells

Journal: Frontiers in Immunology

Publication Date: October 1, 2026

Paper Link: http://doi.org/10.3389/fimmu.2026.1976202