Using these protein “flags” as targets, researchers have developed several different types of immunotherapy. You may have already heard of two of the proteins used as immunotherapy targets: CD38 and SLAMF7. CD38 and SLAMF7 can be found on both myeloma cells and healthy cells, but myeloma cells tend to have them in higher amounts and thus they are useful flags for myeloma cells. The drugs Darzalex and Sarclisa were designed specifically to latch onto CD38. Similarly, the drug Empliciti was designed to latch onto SLAMF7.
Another myeloma cell surface protein that is being used as a target for many different kinds of immunotherapies is called the B-cell maturation antigen, or BCMA. What is especially exciting about BCMA is that—unlike CD38 and SLAMF7—it is found exclusively on myeloma cells. Several types of immunotherapy are being developed for patients with multiple myeloma (these include bispecific antibodies , antibody–drug conjugates [ADCs] , and CAR T-cell therapy ), and most of them target the BCMA protein. Currently, these agents are in the experimental stage of development.
Several different types of antibody are used as antibody therapy, one of which is called a bispecific antibody (or, sometimes, a bispecific T-cell engager or BiTE). Bispecific antibodies are made from pieces of two different antibodies that have been fused together, so that one piece binds to myeloma cells and another piece binds to cells of the immune system.
Most bispecific antibodies target BCMA on myeloma cells and bind to a protein called CD3 that is found on an immune cell called a T cell. The T cell, once attached to the myeloma cell, releases a type of poison that kill(s) the myeloma cell.
Bispecific antibody treatment is not yet approved for use in patients with multiple myeloma, but several are being studied—and showing promise—in clinical trials.
Not only do ADCs target, bind to, and kill myeloma cells directly; they also activate NK cells, which are a special type of cell in the immune system that, once activated, seeks out and destroys myeloma cells by releasing its own cell-killing toxins.
As with bispecific antibodies, ADC therapy for multiple myeloma is still in development and has not yet been approved for use outside of clinical trials. ADCs that target BCMA and have shown promise in clinical trials include belantamab mafodotin, CC-99712, FOR46, MEDI2228, and STRO 001.
Normally, a particular type of white blood cell called a T cell circulates throughout the body. T cells are important in fighting infections and looking for cancer cells. When cancer cells are detected, T cells kill them by grabbing onto and pumping toxins into them. Unfortunately, cancer cells have found ways to “hide” from T cells.
In CAR T-cell therapy, a patient’s white blood cells (including T cells) are collected from their blood, modified in a lab to be more effective in identifying and attacking myeloma cells, and then infused back into the patient—as “supercharged” myeloma fighters. These “supercharged” T cells (from which this type of therapy gets its name) are able to find and kill myeloma cells—even when they’re hiding.
Anti-BCMA CAR T-cells in clinical development include bb2121, bb21217, ALLO-715, Descartes-08/-11, JCARH125, JNJ-4528, NKR-2, P-BCMA-101, and UCARTCS1A.