K-Bio accelerates solid cancer trials with ‘new MOA’ CAR-T

CAR-T, with challenges in locating targeted antigens, commercialization is limited to treating blood cancer

Korean companies pursue solid cancer indication using mesothelin and switching material

HK inno.N, GC Cell, AbClon, and Vaxcell-Bio aim to start clinical trials

The Korean pharmaceutical and biotechnology industry aim to introduce solid cancer-targeting CAR-T with new mechanisms of action (MOA).

 

Chimeric antigen receptor T (CAR-T) cell therapy is an immune cell therapy for cancer treatment designed to deliver genetic material to T cells to produce the CAR in patients.

 

CAR-T has not been approved for indications in solid cancer because the tumor microenvironment, such as fibroblasts in tumor tissues, limits T-cell modifying CAR-T from T-cell infiltration, posing barriers to discovering target antigens.

 

All of the commercialized treatments, including Novartis’ Kymriah, Gilead Science’s Yescarta, and BMS’ Breyanzi, have been approved for blood cancers.

 

To overcome these challenges, Korean companies are developing differentiated strategies, such as targeting mesothelin that can adhere to the cells and aid in signaling or new technology platforms.

 

According to industry sources on the 29th, HK inno.N, GC Cell, AbClon, and Vaxcell-Bio are conducting clinical trials for CAR-T therapy to treat solid cancer.

 

HK inno.N.

 

HK inno.N and CellabMED, a Korean biotechnology company, are developing CAR-T therapy for treating solid cancer.

 

Earlier this month, these companies signed a joint-research agreement to collaborate on new drug development throughout all phases, including research, production, and business development.

 

CellabMED, a biotechnology company, specializes in developing innovative anticancer drugs based on antibody therapy and CAR-T therapy.

 

The company’s CLM-103, a candidate CAR-T targeting glioblastoma, has received IND approval to target solid cancer for the first time in South Korea.

 

HK inno.N is developing CAR-T therapy using T-cells expressing an antibody that inhibits the immune gateway factor ‘HLA-G’ as their inhouse research.

 

HLA-G overexpression on certain cancer cells can disrupt the immune system in the body.

 

HK inno.N’s CAR-T therapy has been selected as a national drug development support project, and it aims to start clinical trials.

 

GC Cell.

GC Cell is developing a CAR-T therapy targeting MSLN (mesothelin), primarily overexpressed in solid tumors.

 

Mesothelin is gaining attention as a target for cancer antigen, with expression rates of 85-90% in mesothelioma, 80-85% in pancreatic cancer, and 60-65% in ovarian cancer and lung cancer.

 

In preclinical studies, GC Cell confirmed the anticancer activity in experiments targeting pancreatic cancer tissue transplanted animals.

 

Additionally, no side effects related to the target or non-tumor toxicity were observed.

 

AbClon.

AbClon is developing a candidate CAR-T therapy, AT501, for patients with solid tumors.

 

AT501 is a switchable CAR-T therapy candidate targeting HER2-positive solid tumors.

 

AbClon's in-house research has developed this therapy by applying existing CAR-T technology to a switch molecule that combines an artificial protein binding to HER2-responsive specific targets and cotinine.

 

AbClon has developed the switchable CAR-T platform (zCAR-T).

 

It is a next-generation technology that uses cotinine switch molecules to regulate CAR-T activity, addressing issues found in conventional therapies, such as toxicity, resistance, and disease expansion.

 

According to the company, the zCAR-T platform is an improved technology that requires switch molecules to attack cancer cells rather than developing CAR-T cells that directly target specific proteins on the surface of cancer cells.

 

This approach has the advantage of activating and proliferating CAR-T cells and altering target molecules using switch molecules.

 

Vaxcell-bio.

Vaxcell-bio is developing ‘VaxCAR2301.’ It is a novel candidate CAR-T therapy that simultaneously targets PD-L1 and EphA2.

 

According to the company, when using the single-chain antibody fragment (scFv) of the immune checkpoint inhibitors avelumab and atezolizumab, which target PD-L1, in immune cell production, either non-dissociation or slow dissociation after cancer cell death can occur, resulting in excessive cytokine storms.

 

The company addressed this issue by reducing the affinity of the antigen-binding site, which binds to antibodies, to a moderate level.

 

In preclinical studies, VaxCAR2301 demonstrated a CAR expression rate reaching 78% in CD8-positive cytotoxic T cells.

 

This is significantly higher than the 58% for avelumab CAR-T and 45% for atezolizumab CAR-T.

 

Additionally, treatment with VaxCAR2301 led to controlled tumor size, rapid weight recovery, and an extended survival period until the end of the experimental observation.