Nanoparticle multispecific T-cell engagers for the treatment of multiple myeloma.

Despite the compelling clinical success of chimeric antigen receptor (CAR)-T cells and bispecific T cell engagers (BiTEs) for the treatment of multiple myeloma (MM), many patients relapse due to tumor escape. A list of limitations exists for both immunotherapies. CAR-T cells, for instance, 1) only target one cancer antigen when it is evidently known that cancer cells express a landscape of heterotypic genes and moieties; and 2) are extremely expensive with a total cost of more than $1 million. With regards to BiTEs, limitations arise from: 1) the inability to target multiple cancer antigens; 2) the need to be continually infused into the patient to enable efficacy and distribution due to their very short half-lives (2 hours); and 3) the increased risk of infections and sepsis-related deaths due to continual infusion. In addition, BiTEs and CAR-T cells require the use of laborious techniques and sophisticated equipment for production. To circumvent these issues, we have developed a nanoparticle in which two antibodies are conjugated to the surface of a liposome; one to recognize an epitope on MM and the other to engage T cells, which we defined as the nanoparticle bispecific T cell engager (nanoBiTE). Moreover, we have made a nanoBiTE with more than three total targeting moieties; one to engage the T cells and the other two or more to target various epitopes on MM, defined as the nanoparticle multi-specific T cell engager (nanoMuTE).