Immuno-oncology is the use of the body’s own immune system to treat cancer. It is considered to be a subset of immunotherapy, which is the more general term used to describe manipulating the body’s immune response in order to treat disease. The immune system is extremely complex (which makes figuring out how best to use the new treatments also very complex) but fundamentally consists of cellular elements (specialized white blood cells including T cells, B cells and macrophages) and non-cellular, or molecular components (antibodies produced by B cells, cytokines, which are proteins and glycoproteins secreted by certain cells to signal other cells, and others).

Different immuno-oncology treatments use different components of the immune system to attack the cancer. Monoclonal antibodies and chimeric antigen receptor therapy (CAR-T) are getting most of the attention right now.

An antibody works by attaching itself to a specific receptor (antigen) on the surface of another cell (which could be a virus, bacterium or cancer cell). This process flags that cell as abnormal and it can then be destroyed by T cells. The tricky thing about cancer cells is that they are sometimes able to “hide” from the normal surveillance of the immune system, allowing the cancer to grow. For example, two proteins designated PD-L1 and PD-L2 can be expressed by cancer cells. These interact with a protein on the body’s T cells and are able to de-activate them so that they no longer recognize and destroy the cancer cells. These substances and others have been identified as critical to stopping the growth of cancerous tumors. The pathways are called “immune checkpoints,” hence the drug class called “checkpoint inhibitors.” BMY’s two drugs, Opdivo and Yervoy, are both checkpoint inhibitors. Another avenue receiving a lot of research attention is CAR-T. In this approach, a patient’s own T cells are removed from the body and have special receptors added to them in the lab. These receptors allow the T cells to recognize the specific cancer being treated and destroy it. The FDA has just approved the first CAR-T, made by Novartis. Kite Pharmaceuticals, recently acquired by Gilead, expects to have its CAR-T approved in November.

Recent research results suggest that combination therapy (more than one drug or a combination of older drugs and newer drugs) may be more effective than single-drug therapy. More work is also underway to identify which patients are likely to respond best to immunologic approaches to cancer treatment.

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