Researchers say they have discovered a new way to target multiple myeloma (MM) and other cancer cells.
The investigators developed human T-cell receptors (TCRs) that have no tolerance toward human cancer antigens and specifically recognize the antigen MAGE-A1, which is present on MM and other cancer cells.
Matthias Obenaus, MD, of the Max-Delbrück-Center for Molecular Medicine in Berlin, Germany, and his colleagues described this work in Nature Biotechnology.
Instead of directly using human-derived TCRs, which do not mediate substantial anti-tumor effects, the researchers took a “detour” by employing a mouse model.
First, they transferred the genetic information for human TCRs into the mice, thereby creating an arsenal of human TCRs.
Then, the investigators isolated the TCRs from the mice and transferred them into human T cells. This “trained” the cells to recognize MM and other cancer cells (eg, melanoma and fibrosarcoma cells) as foreign.
The researchers noted that some people possess T cells that naturally recognize MAGE-A1 on tumor cells, but only in vitro.
In vivo experiments revealed that only the human TCRs derived from mice were effective against tumors. The TCRs derived directly from humans were too weak to recognize the tumor antigens sufficiently.
The investigators said the fact that their mouse-derived human TCRs were more effective is a strong indication that human T cells are tolerant toward MAGE-A1.
Using the TCRs they developed, the researchers are now planning a clinical trial of patients with MAGE-A1 positive MM.
