Therapies that activate the patient’s immune system to destroy cancer are known as cancer immunotherapies. One type of immunotherapy consists of monoclonal antibodies. These are proteins that stick to one specific target typically expressed on cancer cells. Once bound to the cancer cell, monoclonal antibodies activate other parts of the immune system to destroy the cancer cell.
Other types of cancer immunotherapies activate cells called T cells. T cells circulate throughout the entire body until they encounter a cancer cell. Once attached, T cells kill tumor cells and move on to recognize and kill other cancer cells.
Cancer immunotherapies are arguably one of the most promising treatments for patients with advanced cancers such as melanoma and lung cancer. The results of various immunotherapy clinical trials have shown great promise, and immunotherapies are achieving responses never seen before in specific types of cancers. Below are examples of cancer immunotherapies and trials ongoing at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center.
Checkpoint Inhibitors – Taking the Brakes Off the Body’s Immune System
Cancer cells put up defenses so they can’t be detected by the body’s immune system. One of the ways they do this is to render the immune system ineffective by presenting proteins that turn off response from T cells–the immune cells that kill tumor cells. Therapies known as “checkpoint inhibitors” work by blocking these proteins so that T cells can be activated to recognize cancer cells as foreign invaders.
One example of a checkpoint inhibitor is anti-CTLA-4. CTLA-4 is normally expressed on the surface of T cells. Tumor cells can activate the CTLA-4 pathway to suppress T cell activity. However, therapies such as ipilimumab block the CTLA-4 and restore tumor immunity.
Program death-1 (PD-1) is another protein found on the surface of T cells. PD-1 is a negative regulator of T cells and thus inhibits their antitumor responses. PD-1 interacts with PD-L1 and PD-L2 which are found on cancer cells as well as other types of cells within the tumor. Therefore, therapies that block PD-1 (such as pembrolizumab and nivolumab) or PD-L1 (atezolizumab) or PD-L2 can prevent the T cells from becoming suppressed and can reinvigorate antitumor immune responses.
Therapies that help maintain T cell function can also be used alone or in combination with checkpoint inhibitors to increase antitumor T cell responses. One such example is indoximod. Indoximod blocks the enzyme indoleamine 2,3-dioxygenase (IDO). Inhibiting IDO helps maintain high levels of an essential amino acid called tryptophan which is critical for T cell function. Another example is interleukin-2 (IL-2) therapy, a protein or cytokine that helps stimulate various types of immune cells including T cells. IL-2 has been approved for cancer treatment.