Mechanisms of Immunotherapy & Cancer Treatment Options

Instructor: Jennifer Dokas
Cancer immunotherapy, or targeted therapy, uses the patient's immune system (white blood cells, such as T-cells) to treat cancer. In this lesson, you'll learn the mechanism of how cancer cell(s) invade our immune system and how immunotherapies can halt this invasion.

Immune System Response to a Cancer Cell

Our immune system is composed of lymph nodes where white blood cells (WBCs), lymphocytes or T-cells are housed to fight infection, viruses and cancer. Let's think of the immune system as a central firehouse and the lymph nodes as the town firehouses. The firefighters are the WBCs, in particular the lymphocytes or T-cells. The overall response of a firehouse (immune system) is to stop the town fire (cancer cells) with the help of the firefighters (T-cells). Each cell (cancerous or not) has antigens (proteins) on its surface.

Other proteins or medicines bind to the proteins on the cancer or non-cancer cell, thereby inhibiting or stimulating the job of that particular cell. Try to think of the 'medicine' as a person (protein) trying on a glove (other protein on the cancer cell). If the glove fits the on the person's hand, then this 'fit' can either inhibit or activate the cancer cell. Typically, the mechanism of cancer medicine is to inhibit the cell from dividing and spreading in the body.

The last part of the cancer cell death involves the antigen. The cancer cell is destroyed by the antigen presenting cells (APCs), which then activate the cytotoxic T lymphocytes (CTLs), or killer T-cells. The CTLs eradicate the malignant cells (cancer). You can remember this because cytoxic ends in 'toxic,' so think of the CTL as the toxic cancer killer.

Also, think of the APCs as the 'regular army' and the CTLs or T-cells as the 'special forces' in our military. Imagine if one of these mechanisms in the cancer cell death cycle is tricked by the cancer cell. This cycle would be halted and the cancer cells would mutate: grow, divide or spread to other parts/organs in the body.

Cancer Immunotherapies

Let's explore four different cancer immunotherapies.

Cancer Vaccines

Cancer vaccines include tumor-specific or nonspecific antigens; weakened or killed cancer cells; APCs, such as dendritic cells (cells in skin, nose, lung, stomach, and intestines); or DNA that codes (matches) for the antigens of cancer cells.

One example of an APC is the dendritic cell vaccine Sipuleucel-T. It contains one's own activated dendritic cells that stimulate a response against a protein (antigen) that is found on certain cancer tissues.

Once the dendritic cell attaches with another protein, the vaccine is infused (similar to an intravenous infusion) into the patient. The targeted protein on the cancer cell is recognized and killed by the T-cells.

Monoclonal Antibodies

Monoclonal antibodies are proteins that stick to antigens or foreign molecules on a cell. An antibody attaches to an antigen; it recruits other immune cells to kill/eradicate the cancer cell. Alemtuzumab, a monoclonal antibody, binds to a antigen receptor (CD52) on cancer cells and recruits T-cells to eradicate the cancer cell.

Immune Checkpoint Inhibitors

These are molecules or proteins that need to be activated or inactivated to start an immune response. PD-1, a checkpoint protein, is on the surface of T-cells. It binds to the protein receptors (PD-L1) on the T-cells and prevents the T-cells from harming healthy cells. Through this binding, it keeps the T-cells in the 'off switch' (similar to keeping the brakes of a car in the on position).

Cancer cells have many PD-L1 proteins, so they can trick the immune system. Pembrolizumab is a protein (monoclonal antibody) that binds to PD-L1 (protein receptor) and therefore is an immune checkpoint inhibitor. By preventing (blocking) PD-1 from binding to PD-L1, it can enhance the immune system, and cancer cells along with normal cells are killed. By killing normal healthy cells, an autoimmune (against one's immune system) is created that allows for many other viruses and bacteria that are 'normally in check' to flourish.

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