Single-targeted chimeric antigen receptor (CAR) T cells tremendously improve outcomes for patients with relapsed/refractory hematological malignancies and are considered a breakthrough therapy. However, over half of treated patients experience relapse or refractory disease, with antigen escape being one of the main contributing mechanisms. Dual-targeting CAR T-cell therapy is being developed to minimize the risk of relapse or refractory disease. Preclinical and clinical data on five categories of dual-targeting CAR T-cell therapies and approximately fifty studies were summarized to offer insights and support the development of dual-targeting CAR T-cell therapy for hematological malignancies. The clinical efficacy (durability and survival) is validated and the safety profiles of dual-targeting CAR T-cell therapy are acceptable, although there is still room for improvement in the bispecific CAR structure. It is one of the best approaches to optimize the bispecific CAR structure by boosting T-cell transduction efficiency and leveraging evidence from preclinical activity and clinical efficacy.

A team of researchers at the University of Warwick and Monash University has solved a puzzle that has stumped drug developers for decades: how bacteria naturally create multiple versions of powerful cancer therapies. The breakthrough could accelerate the development of new treatments for hard-to-treat cancers.

Harnessing bacterial enzymes to create drug variants, a strategy known as combinatorial biosynthesis, has long been a goal for scientists. But without understanding how these enzymes interact, progress has stalled.

Published in Nature Communications, the researchers have finally revealed how bacterial enzymes communicate and work together to assemble a family of related anticancer compounds. This family includes romidepsin (Istodax), a clinically approved blood cancer treatment. By understanding this “mix-and-match” process and replicating the principle in the lab, the researchers have established an approach to designing new therapies.

¹ Department of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.

²Neuro-Microscopy and Minimally Invasive Translational Medicine Innovation Center, Affiliated Hospital of Nantong University, Nantong, China.

³Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China.