Antibody-cancer drug combo shows promise against aggressive lymphoma

JUPITER, Fla.— Cancer-hunting antibodies coupled with a natural compound found in soil microbes proved a powerful combination against an aggressive type of blood cancer, according to a new study from scientists at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology.

The cancer-killing compound, called tiancimycin, was found within a historic collection of soil microbes housed at the institute. The research team’s antibody-drug combo, or ADC, showed a striking ability to kill aggressive lymphomas while ignoring healthy, noncancerous cells in blood samples donated by cancer patients.

The study, funded by the National Institutes of Health, focused on diffuse large B cell lymphoma, one of the more common, and aggressive, subtypes of white blood cell cancers. The study results appear July 1 in the Journal of the American Chemical Society Au.

 “It would be the ultimate reward if this makes it into the clinic and impacts patient outcomes one day,” said Ben Shen, Ph.D., a chemist who is a member of the UF Health Cancer Center’s Cancer Targeting and Therapeutics research program. Shen directs The Wertheim UF Scripps Institute’s Natural Products Discovery Center, a historic collection of 125,000 microbial strains gathered long ago by pharmaceutical company scientists who were inspired by the discovery of penicillin.

Cancer patients have recently benefited from the emergence of precision cancer treatments, which are targeted to specific genetic mutations. Still, patients face many challenges, especially the threat of drug resistance. Someone’s cancer may respond well to a precision drug for a while, only for it to become less effective over time.

That’s why doctors need many more precision therapies in their arsenal. Patients who have lymphomas, which have many subtypes, need more treatment options. Diffuse large B cell lymphoma is a non-Hodgkin lymphoma that affects around 20,000 people annually in the United States.

Shen said the tiancimycin tested by his team killed the lymphoma, but risked killing other cells, too. Tethering it to a cancer-seeking antibody offered a way to direct a drug specifically where it’s needed. Shen teamed up with a former colleague from The Wertheim UF Scripps Institute, Christoph Rader, Ph.D., to make the antibody-drug combo.

Rader describes the antibody the scientists used to deliver the natural product as a “double-decker bus,” with a targeting antibody linked to an active, drug-carrying antibody. This double-decker antibody approach has been used successfully in lab studies with other payloads, too, Rader noted, including payloads that vanquished aggressive breast cancer cells, multiple myeloma and non-Hodgkin lymphoma cells.

“The compatibility of the conjugation platform with novel payloads discovered in the Natural Products Discovery Center at The Wertheim UF Scripps Institute is exciting and is paving the way to next-generation ADCs for cancer therapy,” Rader said.  “It further documents the versatility of this conjugation platform.”

Scientists from The Ohio State University Comprehensive Cancer Center in Columbus, Ohio, also contributed to the study.

Linking the tiancimycin to Rader’s antibodies required two years of chemistry work. Shen first described that process in a paper published in 2023.

Once the natural products and antibodies were successfully connected, the team’s cell-based testing revealed which form of tiancimycin would be most effective against the cancer. The process and the platform the team developed to create this ADC could prove valuable in developing next-generation immunotherapies that target various cancers and mutations, Shen said. His next step is to test the ADC in mice.

“Taken together, the data suggest that this combination of engineered payload, linking chemistry and ‘double-decker’ antibodies could one day offer a promising new option for lymphoma patients,” Shen said.