Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers on cancer cells in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in multiple myeloma clinical trials include:
- BCMA: an important signaling receptor found mainly on mature B cells; often expressed by lymphoma and myeloma cells
- CD19: a receptor found on the surface of almost all B immune cells that influences their growth, development, and activity; often expressed by leukemia, lymphoma, and myeloma cells
- CD20: a receptor found on the surface of B immune cells during their development; often expressed by leukemia, lymphoma, and myeloma cells
- CD38: an immune cell surface protein that plays roles in cell adhesion and signaling; often expressed by leukemia and myeloma cells
- CD52: a protein found on the surface of mature immune cells as well as other cell types
- EGFR: a pathway that controls cell growth and is often mutated in cancer
- HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
- SLAMF7: a surface protein found on plasma B cells; often expressed by lymphoma and myeloma cells
Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in multiple myeloma clinical trials include:
- MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but can become reactivated in cancer cells, flagging them as abnormal to the immune system
- Survivin: a protein that can prevent cellular death and is overexpressed by a number of cancer cell types
- Telomerase: an enzyme that helps maintain the health of cellular DNA; exploited by cancer cells to achieve immortality
- Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels
- WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)
Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in multiple myeloma clinical trials include:
- BCMA: an important signaling receptor found mainly on mature B cells; often expressed by lymphoma and myeloma cells
- CD19: a receptor found on the surface of almost all B cells that influences their growth, development, and activity; often expressed by leukemia, lymphoma, and myeloma cells
- CD20: a receptor found on the surface of B cells during their development; often expressed by leukemia, lymphoma, and myeloma cells
- NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer
- WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)
Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in multiple myeloma clinical trials include:
- CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
- IL-2/IL-2R: activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
- PD-1/PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted,” and can restore the activity of already-exhausted T cells
- Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors
Oncolytic virus therapy uses viruses that are often, but not always, modified in order to infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in multiple myeloma clinical trials include:
- Measles virus: a highly contagious virus that infects the respiratory tract and can cause measles
- Reovirus: a family of viruses that can affect the gastrointestinal and respiratory tracts in a range of animal species
- Vesicular stomatitis virus: a virus that belongs to the same family as the rabies virus; can cause flu-like symptoms in humans