Chimeric Antigen Receptor (CAR) T cell therapy has shown remarkable success in blood malignancies. However, its application in solid tumors has been hindered by a significant challenge: the lack of tumor-specific antigens (TSAs). This limitation causes CAR-T cells to infiltrate and attack non-malignant tissues that express tumor-associated antigens, leading to severe on-target off-tumor toxicity. This issue has been widely observed in clinical trials and underscores the urgent need for innovative strategies to mitigate it.
In response to this challenge, Immunofoco Biotechnology has partnered with Professor Bo Zhai—currently the Director of the Center for Minimally Invasive Interventional Therapy at Tongji University Affiliated Dongfang Hospital—and his team from Renji Hospital, Shanghai Jiao Tong University, to develop the groundbreaking Peri Cruiser® technology platform. This platform modulates the distribution of CAR-T cells within the body, significantly reducing on-target off-tumor toxicity caused by tumor-associated antigens (TAAs) in normal tissues. It not only retains the ability of CAR-T cells to target primary tumors but also effectively controls tumor metastasis, marking a breakthrough in the application of CAR-T therapy for solid tumors. This research was published on January 22nd in the prestigious journal Science Translational Medicine and featured as the cover article, highlighting a significant milestone for Immunofoco in solid tumor CAR-T therapy.
The Peri Cruiser® technology platform is based on a multi-shRNA approach that enables the expression of CAR and the knockdown of multiple key adhesion and migration molecules in T cells on a single lentiviral vector. This innovation significantly reduces the toxicity of CAR-T cells in normal tissues, as demonstrated by reduced infiltration into organs such as the liver and lungs, while preserving their ability to infiltrate tumors.
A variety of in vitro experiments, including continuous killing assays, have demonstrated that reducing the expression of adhesion molecules can enhance the sustained cytotoxicity of CAR-T cells against tumors. This reduction also lowers the expression of exhaustion markers and increases the proportion of memory cells. Importantly, it does not affect the formation of immunological synapses between CAR-T cells and tumor cells. These findings highlight the multiple advantages of this technology platform.
Researchers have also conducted in vivo efficacy studies in colorectal and gastric cancer models. The Peri Cruiser® platform demonstrated robust anti-tumor activity, retaining the ability to inhibit various solid tumors and metastatic tumors. This study not only presents a novel approach to CAR-T technology but also offers a solution for safer and more effective CAR-T therapy in solid tumors.
Dr. Sun Minmin, founder, chairman, and CEO of Immunofoco Biotechnology, pointed out that expanding cell therapy applications for solid tumors poses significant challenges, especially the potential on-target off-tumor toxicity, which limits CAR-T target selection and application in various solid tumors. Immunofoco is a company dedicated to breaking through solid tumor cures and bringing long-term survival benefits to global patients through the development of immune cell therapy drugs. Our Peri Cruiser® technology platform offers a new solution to address the bottleneck issues in expanding CAR-T therapy applications for solid tumors. This represents not only an important milestone in the breakthrough of our company's technology platform but also a solid step towards our vision of curing solid tumors. In the future, we will continue to collaborate with medical experts to accelerate the pace of technology transfer and application. We remain patient-centered, dedicated to promoting safer and more efficient immune cell therapy solutions that benefit patients worldwide.
About Immunofoco
Immunofoco has pioneered a clinical strategy focused on "curing the solid tumors by treating them as hematologic malignancies", addressing the challenges in solid tumor treatment, and the clinical advantages of treating hematologic malignancies. To improve the safety of CAR-T products, counteract tumor heterogeneity, and to enhance their effectiveness in tumor amplification and infiltration, we have developed innovative platforms such as Peri Cruiser®, SNR, and T-Booster. Driven by the clinical outcomes, our company maintains an extensive spectrum of product pipeline. Notably, our IMC002 (CLDN18.2 CAR-T) has been granted Fast Track designation and orphan drug designations (ODDs) for gastric and pancreatic cancers by the U.S. FDA, and its IND application received approval in both the United States and China in April 2023. Similarly, our IMC001 (EpCAM CAR-T) product obtained ODD from the U.S. FDA in August 2023, and its IND application has been approved in both the U.S. and China in February 2024. The IMC008 (SNR CAR-T) product has rapidly moved to the IIT stage and received two ODD approvals from the U.S. FDA in August 2023, for the treatment of gastric cancer and pancreatic cancer, respectively. Embodying the ethos of "collaboration, aspiration, and dedication for the best clinical results," our company brings together industry talents and experts to develop innovative cell therapies that offer enduring survival benefits for patients with solid tumors. For further details about Immunofoco, please visit our website at www.immunofoco.com.
