바이오스펙테이터

바이오스펙테이터 Euna Lee 기자

Established in February this year, Korea's first CAR-T development company, DLBCL patient target, target of clinical 1 / 2a launch in 2020

▲국내 첫 CAR-T 치료제 전문 개발회사 큐로셀의 임직원들. 심현보 교수(왼쪽부터), 김찬혁 교수, 김건수 대표, 윤순옥 과장, 이형지 연구원, 이상훈 연구원.

"Curocell’s mission is to discover and develop an innovative chimeric antigen receptor (CAR)-engineered T cell therapy that may interfere with inhibitory function of immune checkpoint receptors such as CD19 in oncology. To this end, we are mainly focusing on new CAR design to expand the use of CAR T-cell therapy and address tumor’s antigen escape mechanism from targeted immunotherapy,” Kim Geon-soo, CEO of Curocell, commented.

With respect to the company’s novel modality strategy different from other CAR-T cell therapies, CEO Kim noted that “Our novel CAR design will yield better efficacy in B cell malignancies compared to other CAR T-cell therapies".

Founded in February this year, Curocell is dedicated to developing CAR T-cell therapy for the first time in Korea by targeting hematological malignancies such as diffuse large B cell lymphoma (DLBCL) and multiple myeloma (MM) that are known to have poor prognosis.

To date, CAR T-cell therapies have generated impressive results and considerable promise for some blood cancers, with up to 80% complete remission rate. Nevertheless, possible side effects including neurotoxicity, cytokine-release syndrome (CRS), and less efficacy for solid tumors have emerged as main challenges to broad application of CAR T-cell therapy, let alone high manufacturing costs.

To overcome these drawbacks, a number of companies have attempted to examine a new proof of concept on CAR T-cell. As a result, over 100 clinical trials are being globally conducted. Unfortunately, Korea has little clinical experience in CAR research hitherto mainly because local companies cannot effectively undertake their preclinical and clinical developments due to the lack of professionals with extensive experience in CAR research. Now, Curocell is at the forefront of making a strong push toward the development of an innovative CAR-T cell therapy for solid tumors.

Kim revealed that “To make CAR T-cell therapy a viable option for patients with terminal cancer, we established Curocell with concerted efforts of professionals in industry and academia. We are aiming to develop and commercialize an innovative CAR T-cell therapy with strong technical advantages under our own preclinical and clinical development programs in Korea.”

Curocell’s board of directors and researchers are experts from various industrial and academic sectors with rich experience and expertise as shown below.

• CEO Kim was engaged in R&D strategy and planning projects of Hanwha Chemical, LG Life Sciences, and CHA Biotech;

• Professor Kim Chan-hyeok was involved in CAR research from Scripps Research Institute and California Institute for Biomedical Research (Calibr);

• Professor Shim Hyun-bo, Ewha’s Women University, is an expert in antibody research;

• Patent attorney Kwon Yong-jun is screening patents of global competitors on real-time basis.

Professor Shim is responsible for developing a newly designed CAR containing an optimal single-chain variable fragment (scFv) of antibody that can recognize tumor cells from CAR T-cell. Professor Kim focuses on CAR platform development. CEO Kim is involved in the commercialization of CAR T-cell therapy as well as the development of pipeline drugs, manufacturing process, and preclinical and clinical developments. In addition, Curocell’s researchers have vast experience in a broad range of viral vaccines, immune cells, and animal experiments that are vital to CAR T-cell platform development.

The fact that a combination of CAR T-cell therapy with an immune checkpoint inhibitor may further potentiate anti-tumor effects is drawing Curocell’s keen attention. Curocell plans to develop CD19-targeted CAR T-cells that might be indicated for DLBCL using an approach to effectively limit the inhibitory function of immune checkpoint receptors. In particular, studies have showed that 24% of patients with DLBCL have T-cells that express PD-L1, one immune checkpoint receptor, from their cancer or adjacent cells. “Curocell is developing CD19-targeted CAR T-cells that can modulate immune checkpoint receptor and yield good clinical outcome,” Kim revealed.

Curocell’s main target in the development of innovative CAR T-cell therapy is non-Hodgkin lymphoma (NHL) including DLBCL known to have poor prognosis.

Professor Kim said, “If you have a novel idea on CAR T-cells, easily modified CAR platform may facilitate clinical development”. He explained that technically innovative companies would be able to develop their own CAR T-cell therapy.

CAR T-cell therapy involves removing some T-cells from a patient's blood. Researchers will then tweak the outside of each cell in the lab by adding a receptor called CAR. When these altered T-cells are infused back into the body, these receptors can help T-cells find and kill cancer cells. It usually takes approximately three weeks from CAR T-cell’s mass production, including freezing procedures, to its final manufacture for commercial use.

“Unlike current biopharmaceutical products that require a mass-scale production system, CAR T-cell therapy can be made available in a small-size GMP facility with a production capacity of 5-10 liters per patient,” CEO Kim said. He added that “Local clinical trials can be conducted through close collaboration with hospitals.”

Curocell is currently screening CAR T-cell candidates to block the mechanism involved in tumor antigen escape. Their therapeutic effects for DLBCL and MM will be tested in preclinical trials. The company is aiming to conduct phase I and 2a trials for its leading pipeline product against DLBCL, anti-CD19 CAR T-cell therapy, in 2020.

With its own development program for CAR T-cell therapy based on their GMP facility, Curocell has revealed its plans to promote Korea’s medical tourism business to attract patients from China and Japan via collaboration with large hospitals in metropolitan areas. For possible technology transfer, the company will also conduct its translational research and animal experiments for a promising CAR T-cell therapy that is effective for cancers frequently found in the U.S. and Europe.

Expressing his strong desire to discover and develop an innovative CAR T-cell therapy to address unmet medical needs, CEO Kim said that “CAR T-cells therapy is a hope and final treatment option for terminal cancer patients. We are committed to expediting the development and review of groundbreaking treatments that have the potential to be life-saving for patients whose cancer has been considered terminal.”