Monoclonal antibodies (mAbs) have several binding regions. When our mAbs are infused into a person, two of the regions bind to specific antigens on target cells in the body (the cancerous cell, or myeloma plasma cell). Once this binding occurs, a natural killer (NK) cell from the immune system binds to the third region of the antibody. This binding activates the NK cell, which results in killing of the cancerous cell.
It is important to note that, as demonstrated above, HaemaLogiX's monoclonal antibodies do not bind to healthy plasma cells, thus leaving them unharmed and able to function normally.
Several drugs that are currently in use to help treat Multiple Myeloma can be used with our antibodies to help make them more effective at killing the cancerous cells. Giving a patient an immunomodulatory imide drug (otherwise known as an IMiD), such as lenalidomide or pomalidomide will make the cancerous plasma cell express more of our target antigen (either KMA or LMA) on its cell surface. Hence, when our antibodies are infused into the patient, the cancerous plasma cell now has a much greater number of target antigens for our antibodies to bind to. This makes our antibodies much more effective at attaching to the cancerous cell and recruiting the NK cells to kill the cancerous cells. This increase in antigen number following pre-treatment with an IMiD is a mechanism that is unique to our KMA and LMA antigens in multiple myeloma.
CAR T cell Therapies
With CAR T cell therapy, a patient's own white blood cells are collected during a process called apheresis. Once apheresis is complete, the white blood cells are then cultured in a manufacturing facility, where they are modified. During this process, specific genetic code is introduced into the T cells using a viral vector. This genetic code causes the T cells to express our antibody on their cell surface; this expressed antibody on the T cell surface will specifically target the antigen on the cancerous plasma cells. These CAR T cells are then cultured to increase in numbers to billions of CAR T cells and infused into the same patient they came from, where they target and kill the cancerous plasma cells. CAR T cells are frequently used in a patient for whom all other treatments or standards-of-care no longer work.
A bispecific antibody is designed to bind an antigen at one end, and a T cell at the other end. As shown above, the top two arms of the antibody bind to the antigen on the cancerous cell, and the bottom arm binds to a T cell. This binding initiates an immune response that is very effective at killing those cancerous cells.