A collaborative research effort between the university of Calgary and the Heidelberg University Hospital led to an important study published in Cancer Cell, showing that treatment response in patients with multiple myeloma (MM) undergoing bispecific T-cell engager (TCE) therapy, is determined by the expansion of certain pre-existing T-cell clones.
“We are the first researchers to have tracked patient T cells and their response to TCE therapy over time and were able to thus describe how TCE might work in humans” explained the lead author Mirco J. Friedrich, MD, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts.
Longitudinal bone marrow biopsies and peripheral blood draws were performed on patients receiving TCE therapy, enabling analyses of the immune repertoire during therapy.
Dr. Friedrich and his colleagues developed an analysis method to predicting response “based on a patient’s individual T-cell landscape,” and therefore identify patients who may benefit from therapy with bispecific antibodies versus those who may not respond or could develop resistance potential responses.
The authors also found that the induction of major histocompatibility complex (MHC) class I in tumor cells could be of therapeutic benefit. “This represents a potential immune evasion strategy which directly builds on the TCE mechanism of action, and we can now monitor and eventually exploit it to improve long term responses”, Dr. Friedrich added.
Friedrich, M. J. et al. The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients. Cancer Cell https://doi.org/10.1016/j.ccell.2023.02.008 (2023).