Researchers at the Washington University School of Medicine have developed nanoparticle-based bispecific T-cell engagers (nanoBiTEs) and a nanoparticle that targets multiple cancer antigens (dubbed a nanoMuTE) that they say may offer a solution to the major limitations of existing immunotherapy technologies––specifically, poor pharmacokinetics and the ability to target only one antigen on cancer cells. They describe the new platform in a paper published in January in Leukemia.
The nanoBiTEs are described as “liposomes decorated with anti-CD3 monoclonal antibodies (mAbs).” The nanoMuTE “targets multiple cancer antigens by conjugating multiple mAbs against multiple cancer antigens for T-cell engagement.” The nanoparticles’ 60-hour half-life enables once-weekly administration instead of continuous infusion, the authors say, while maintaining efficacy both in vitro and in vivo. Multiple antigen-targeting nanoMuTEs showed greater efficacy in myeloma cells in vitro and in vivo than nanoBiTEs targeting a single antigen. In contrast with nanoBiTEs, treatment with nanoMuTEs did not cause downregulation of a single antigen and prevented antigen-less tumor escape.
This novel platform provides “a relatively easy-to-make and off-the-shelf solution to circumvent the major limitations of the current immunotherapy technologies (CAR T-cells and BiTEs),” the authors write. “The flexibility of the nanoparticle-based immuno-engaging technology provides a general platform with groundbreaking translational potential for developing easy-to-make, specific, and efficacious immunotherapy for cancer in general.”
– Alhallak K, Sun J, Wasden K, et al. Nanoparticle T-cell engagers as a modular platform for cancer immunotherapy [published online ahead of print, 2021 Jan 21]. Leukemia. 2021;10.1038/s41375-021-01127-2. doi:10.1038/s41375-021-01127-2