T cell bispecific antibody cancer therapies gaining traction in Korea

Targeted cancer therapies such as T cell bispecific antibodies, sometimes called bispecific T cell engagers, have been attracting more attention for their ability to hone in on the cancerous cells, and domestic companies are ready to get in on the action.

Last year, the U.S. FDA approved Immunocore’s Kimmtrak (ingredient: tebentafusp) as the first T cell receptor (TCR) therapeutic for patients with HLA-A*02:01-positive uveal melanoma.  Additionally, the FDA  granted approval to Johnson & Johnson’s Tecavyli (ingredient: teclistamab-cqyv), another kind of T cell-mediated checkpoint inhibitor to treat relapsed or refractory multiple myeloma among adults,  last year. 

Aprogen, a Korean company specializing in innovative biological drug development, announced on Wednesday that it registered a domestic patent for an immune checkpoint inhibitor for cancer. 

In particular, the patent is related to an antibody that binds to a protein that regulates immune cell development and differentiation of the cell surface protein, leukosialin, also known as sialophorin or CD43. 

According to the company, the patented antibody is unique among leukosialins as it selectively and strongly binds only to immune cells that are not fully differentiated and have transformed into cancer cells. 

Consequently, the antibody can be used to target abnormally differentiated or cancerous immune cells without affecting normal, fully differentiated immune cells, explained a company official.

The company is applying its bispecific-antibody platform, CHIMPS, which stands for Correlated and Harmonious Interfacial Mutation between Protein Subunits to develop T cell-mediated bispecific antibodies .

By minimizing the number of amino acids that are substituted to create a bispecific antibody, the platform enables the antibody to exhibit high thermostability while maintaining its biological function related to antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). As a result, bispecific antibodies made using CHIMPS technology are superior as they carry the same structure as naturally occurring antibodies, and therefore have the same advantages as antibody drugs.

Currently, Aprogen is developing three bispecific antibodies, AP60 for colorectal cancer, AP10 for blood and solid cancers, and AP70 for acute myeloid leukemia which are currently sitting in the discovery stage.

Still, most of the globally approved antibody therapeutics are monoclonal antibodies that recognize one target and show therapeutic efficacy by targeting angiogenic factors, cancer cell surface receptors, and immune-checkpoint molecules that inhibit T cell activity. However, single-target-based therapies demonstrate limited efficacy in diseases with complex pathogenesis, such as cancer.

According to a recent publication by Nature last year, approximately 30 percent of T cell engaging bispecific antibodies are in clinical trials for treating hematological malignancies but due to poor T cell infiltration in solid tumors, these T cell therapeutics demonstrate a higher likelihood of on-target off-tumor toxicities.

"T cell bispecific-antibodies are designed to allow the bispecific antibody to act as a bridge between cancer cells and killer T cells so that the killer T cells can selectively kill only cancer cells,” explained an Aprogen company official.