[Bio Story]② Big Pharma Exits CAR-NK... K-Biopharma Takes Another Shot with Gastric and Brain Cancer Treatments

Takeda and other pharma giants halt development after failing to demonstrate efficacy in blood cancers
GC Cell to conduct clinical trials for stomach and breast cancer using advanced regenerative medicine
VigenCell to begin Phase 1 brain tumor trial of gene-edited CAR-NK therapy

VigenCell is also accelerating its push into the chimeric antigen receptor natural killer cell (CAR-NK) market, even as global pharmaceutical giants have taken a step back. The company plans to begin a Phase 1 trial next year for its CAR-NK therapy VC302, targeting brain tumors. In animal studies, all the tumors disappeared, and the company plans to test whether the results can be replicated in humans.

CAR-NK is a field that even global pharmaceutical giants have struggled to break into. In clinical trials of CAR-NK therapies for blood cancers, global pharmaceutical companies were unable to demonstrate better efficacy than chimeric antigen receptor T-cell (CAR-T) therapies, leading to a series of development cancellations. Solid tumors, in particular, are a cancer type with notably few competitors in the CAR-NK treatment field. This reflects the difficulty of the challenge, and VigenCell’s strategy is to target precisely this area.

According to industry sources on October 19, global pharmaceutical giants have successively withdrawn from CAR-NK development over the past three years. Janssen terminated a co-development agreement with Fate Therapeutics in January 2023, worth up to $3 billion (approximately 4.032 trillion won). In June 2024, Merck & Co. (MSD) terminated a solid-tumor CAR-NK co-development agreement worth up to $1.86 billion (approximately 2.5 trillion won) that it had signed with Artiva, an affiliate of GC Biopharma, in January 2021. Takeda halted development of its blood cancer CAR-NK therapy TAK-007 in May of the same year and withdrew from the cell therapy business in October last year.

CAR-NK therapies are made by equipping natural killer (NK) cells with chimeric antigen receptors (CARs) that recognize cancer cells. Unlike CAR-T therapies, which are made from a patient’s own cells, CAR-NK therapies can be mass-produced in advance using NK cells obtained from healthy donors or stem cells. They also carry a lower risk of immune-related side effects than CAR-T therapies, and were once considered the next generation of “off-the-shelf cell therapies.”

However, they failed to surpass CAR-T therapies because their effects did not last long in blood cancer trials. Takeda discontinued development of TAK-007 for blood cancers based on clinical trial data, while U.S.-based Nkarta moved its candidate down its development priority list after results from an acute myeloid leukemia (AML) trial fell short of expectations. Takeda, Nkarta, and Fate shifted their CD19 CAR-NK programs to autoimmune diseases such as lupus. In autoimmune diseases, they found a potential path forward by targeting only the problematic B cells.

Solid tumors present an even higher barrier. CAR-NK cells do not readily penetrate tumor tissue, do not survive long in the body, and lose their effectiveness in the immunosuppressive environment around tumors. Most CAR-NK programs targeting solid tumors remain in preclinical or early Phase 1 stages.

VigenCell’s strategy is to use gene editing to address all three limitations at once with VC302. The company added genes that help NK cells travel to tumors and remain active in the area around them. In an experiment involving six mice, all the tumors disappeared. “NK cells are inherently capable of killing cancer cells,” said VigenCell CEO Ki Pyeongseok. “We believed they would perform their role if we gave them the right signals with precision, and we confirmed this in our experiment.”

The remaining challenge is obtaining data in humans. To demonstrate the potential of CAR-NK for solid tumors, the effects observed in animal studies must also be seen in patients. Securing human data first could give the company a stronger position in technology licensing negotiations. The Phase 1 trial of VC302, set to begin next year, is expected to be the first test.

This content was produced with the assistance of AI translation services.