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 esophageal cancer clinical trials include:
- cMET: a growth-related pathway that is often abnormally activated in cancer
- Claudin 18.2: a surface protein overexpressed in some esophageal cancers and involved in invasion and survival
- DKK1: a secreted protein involved in migration, self-renewal, and blood vessel formation
- EGFR: a pathway that controls cell growth and is often mutated in cancer
- FGF/FGF-R: a pathway that controls cell growth, death, and migration
- HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
- TROP2: a protein that is commonly overexpressed in cancer and appears to aid cancer cell self-renewal, proliferation, invasion, and survival
- VEGF/VEGF-R: a pathway that can promote blood vessel formation in tumors
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 esophageal cancer clinical trials include:
- Human Papilloma Virus (HPV)-related antigens: foreign viral proteins expressed by HPV-infected cancer cells
- Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
- 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
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 esophageal cancer clinical trials include:
- Claudin 18.2: a surface protein overexpressed in some esophageal cancers and involved in tumor invasion and survival
- Epstein-Barr Virus (EBV)-related antigens: foreign viral proteins expressed by EBV-infected cancer cells
- 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
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 esophageal cancer clinical trials include:
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 esophageal cancer clinical trials include:
- Adenovirus: a family of common viruses that can cause a wide range of typically mild effects including sore throat, fatigue, and cold-like symptoms
- Maraba virus: a virus found exclusively in insects