Ash 2020 – US academics target the Car-T relapse problem
Lack of persistence remains a problem for BCMA-targeted Car-T therapy, but the US NCI reckons it has an answer. The group is working on FHVH-BCMA-T, a construct that uses as the binding region a heavy chain antibody domain, which is smaller and simpler that the usual ScFv domain that most others use. At Ash Dr Lekha Mikkilineni reported an impressive 90% overall remission rate in 20 multiple myeloma subjects across all five FHVH-BCMA-T doses, of which the fourth, six million cells/kg, was determined to have the best mix of efficacy and safety. Dr Mikkilineni said FHVH-BCMA-T could avoid unwanted immune system responses against linkers and ScFv junctions, because heavy chains do not have any, and the fact that a fully human binder is used could further reduce alloreactivity and cut relapse while cells continue to express BCMA. Nevertheless, only 10 of the 18 remissions are ongoing, patients presumably relapsing because of loss of the BCMA antigen. The lack of durability problem is far from solved.