Current immunotherapy approaches for Esophageal Cancer can be broken into these 5 categories:

1. Checkpoint Inhibitors / Immune Modulators
2. Adoptive Cell Transfer (ACT)
3. Monoclonal Antibodies (mAbs)
4. Therapeutic Vaccines
5. Cytokines

1. CHECKPOINT INHIBITORS / Immune Modulators:
A promising avenue of clinical research in esophageal cancer is the use of immune checkpoint inhibitors. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses. Several checkpoint inhibitors, targeting multiple different checkpoints, are currently in development.

Current agents:
A) Nivolumab (Opdivo), also called ONO-4538, a PD-1 antibody, for patients with unresectable advanced or recurrent esophageal cancers B) Pembrolizumab (Keytruda, MK-3475) for patients with advanced esophageal or esophagogastric junction cancer that progressed after first-line therapy
C) LAG525, is an antibody that targets LAG-3, +/- PDR001, a PD-1 antibody, in patients with advanced cancer, including esophageal cancer

2. ADOPTIVE CELL THERAPY (ACT):
Another major avenue of immunotherapy for esophageal cancer is adoptive T cell transfer. Here, T cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several trials of adoptive T cell transfer techniques are currently under way for patients with esophageal cancer.

Current approaches:
A) Taking enriched tumor-infiltrating immune cells and re-infusing them in patients with metastatic digestive tract cancers, including esophageal cancer
B) Using T cells genetically reengineered to target the NY-ESO-1 antigen in patients with NY-ESO-1-positive cancers. NY-ESO-1, a tumor-associated antigen, is not found on normal cells, with the exception of the testis.
C) Using T cells genetically reengineered to target the anti-MAGE-A3-DP4 protein in advanced cancer

3. MONOCLONALL ANTIBODIES (mAbs):
mAbs are molecules, generated in the lab, that target specific antigens on tumors. Many mAbs are currently used in cancer treatment, and some appear to generate an immune response. Several mAbs are currently being tested in clinical trials.

Current agents:
A) Nimotuzumab, an antibody designed to bind and inhibit signaling from EGFR, in patients with metastatic esophageal cancer
B) IMMU-132, an antibody-drug conjugate targeting Τrop-2, in patients with esophageal and other cancers
C) HuMax, an antibody-drug conjugate targeting tissue factor, in patients with solid tumors, including esophageal cancer

4. Therapeutic VACCINES:
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. One trial is currently enrolling patients.  A vaccine that targets the NY-ESO-1 protein in patients with advanced cancer whose cancers express NY-ESO-1

5. CYTOKINES:
Cytokines are messenger molecules that help control the growth and activity of immune system cells. Interleukin 12 (IL-12) is being tested in patients with solid tumors

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