Cancer researchers have long sought a therapeutic option for people with T-cell lymphomas and leukemias who express the TRBC2 variant of the T-cell receptor — about half of the roughly 100,000 people worldwide affected annually by these blood cancers.

T-cell malignancies, rare and scientifically complex, have received far less pharmaceutical investment than B cell leukemias and lymphomas and have fewer treatment options. As a result, adults with relapsed T-cell cancers have five-year survival rates of 7% to 38%.

“This is a challenging situation because unlike B-cell therapies — where eliminating both cancerous and healthy B cells is tolerable — therapies targeting T cells must preserve enough normal T cells for patients to survive infections,” says Suman Paul, associate professor of oncology.

His team at the Johns Hopkins Kimmel Cancer Center recently reported development of a new treatment that selectively targets TRBC2-positive T-cell cancers, expanding a precision approach they established in 2024 for TRBC1-positive tumors. The therapy, an antibody-drug conjugate (ADC), targets a protein expressed on the surface of T-cell cancers to deliver a cancer cell-killing drug.

In laboratory studies using cancer cell lines and animal models, they found the new ADC to be highly specific to TRBC2 cancers, clearly distinguishing between TRBC2-positive and TRBC1-positive normal T cells. The ADC killed TRBC2-positive cancer cells, leading to robust tumor regression in animal models with minimal toxicity.

“The development of TRBC1 and TRBC2 antibodies together now provides a conceptual ‘matched set’ of precision tools for the great majority of patients with T-cell cancers,” says Paul, senior author of the study, reported recently in Nature Cancer.