Over the past decade, chimeric antigen receptor T cell (CAR-T) therapy has emerged as a groundbreaking approach for treating certain types of cancers. In CAR-T therapy, a patient’s own T cells are genetically modified to express artificial receptors called chimeric antigen receptors (CARs) that target specific proteins on tumor cells. Once reinfused into the patient, these CAR T cells can proliferate and lead to long-lasting antitumor activity. Pioneering CAR-T therapies such as Kymriah and Yescarta have shown impressive results against certain hematologic malignancies like lymphoma and leukemia. Recently, South Korean researchers have made substantial progress in developing promising next-generation CAR-T therapies with improved safety and efficacy.
Novel Techniques to South Korea Car-T Cell Therapy
Several South Korean companies and research institutions are working on enhancing CAR-T cell function and persistence through novel genetic engineering techniques. For example, Anthropic is developing CAR-T cells co-expressing immune checkpoint inhibitors to overcome immunosuppression in the therapy tumor microenvironment. This allows the CAR-T cells to remain active for longer durations. Another approach involves co-expressing memory-boosting molecules like IL-7 and IL-15 along with the CAR construct. This induces memory-like properties in CAR-T cells to provide long-lasting antitumor immunity. Scientists at Yonsei University are investigating adding additional co-stimulatory domains to CARs to enhance T cell activation and proliferation upon antigen recognition. Such multi-armed CARs have shown stronger antitumor effects in preclinical models compared to first-generation CARs.
Tackling Solid Tumors with Novel Targets
While CAR-T therapies have had impressive results against hematologic cancers, treating solid tumors presents unique challenges due to heterogeneous antigen expression and immunosuppressive microenvironments. South Korean researchers are developing CAR-T cells targeting novel solid tumor-associated antigens. A team from Samsung Medical Center engineered CAR-T cells targeting the Oncofetal antigen 5T4, which is overexpressed in various solid tumors including lung, breast and ovarian cancer. In mouse models, these 5T4-CAR T cells showed potent antitumor activity against 5T4-positive tumor xenografts with no signs of on-target off-tumor toxicities. Another target under investigation is GPC3, which is highly expressed in hepatocellular carcinoma (HCC). GPC3-targeted CAR-T cells developed by CHA Biotech demonstrated complete tumor eradication in HCC mouse models without affecting normal tissues. Such novel antigen targets hold promise for safely treating certain solid tumor types.
Addressing Safety Concerns
Despite their clinical benefits, CAR-T therapies can potentially cause life-threatening cytokine release syndrome (CRS) and neurological toxicities due to excessive T cell activation and proliferation. To improve safety, researchers are engineering “suicide genes” into CAR-T cells. One approach involves expressing inducible caspase 9, which can trigger rapid CAR-T cell apoptosis upon administration of a small molecule drug. This provides a “safety switch” in case severe adverse events occur. Another suicide gene strategy used by BioStorage Technologies involves encoding herpes simplex virus thymidine kinase (HSV-TK) within CAR-T cells. If needed, administration of ganciclovir can selectively eliminate HSV-TK-expressing CAR-T cells from the body. Such safety modification strategies could help manage treatment-related risks from overly exuberant CAR-T cell activation.
Large-Scale Manufacturing Capabilities
With several CAR-T therapies entering clinical testing in South Korea, robust manufacturing infrastructure is essential for producing sufficient cell therapy doses. Over the past few years, South Korean companies like Anthropic, GC Pharma and CB Therapeutics have invested heavily in building state-of-the-art Good Manufacturing Practice (GMP) compliant cell therapy manufacturing facilities. These facilities are equipped with closed automated systems for scalable CAR-T production under aseptic conditions. Some can output over 1000 CAR-T batches annually. South Korean GMP regulations also align closely with international standards. These world-class manufacturing platforms enable cost-effective, large-scale CAR-T cell production to meet the growing clinical and commercial demands. Several South Korean CAR-T programs are transitioning from academic medical centers to being produced at these specialized Good Manufacturing Practice (GMP) cell therapy manufacturing facilities.
With a robust CAR-T R&D pipeline and advanced manufacturing capabilities, South Korea is well-positioned to commercialize next-generation CAR-T therapies and make them accessible to broader patient populations. Ongoing clinical trials are evaluating the efficacy and safety profile of novel CAR designs addressing solid tumors, targeting alternative antigens and incorporating safety switches. If successful, these programs could pave the way for ing authorization of safer and more effective ‘off-the-shelf’ CAR-T therapies manufactured on an industrial scale. South Korea’s focus on addressing key challenges in CAR-T development promises to accelerate the realization of this transformative cell therapy’s full potential to cure various cancer types.