Immunotherapy: How One’s Own Body Can Learn to Fight Cancer

Your immune system is designed to eliminate dangerous elements from your body. In addition to removing viruses and bacteria, it often also eliminates potentially cancerous cells. But when, through mutation, healthy cells become cancerous cells, they can often evade detection by the immune system. In some cases, this evasion is done using the same mechanisms normal cells use to prevent autoimmune diseases, and once the evasion is successful, those cancerous cells are free to grow and multiply, threatening your health.

Immunotherapy: How One’s Own Body Can Learn to Fight Cancer

Your immune system is designed to eliminate dangerous elements from your body. In addition to removing viruses and bacteria, it often also eliminates potentially cancerous cells. But when, through mutation, healthy cells become cancerous cells, they can often evade detection by the immune system. In some cases, this evasion is done using the same mechanisms normal cells use to prevent autoimmune diseases, and once the evasion is successful, those cancerous cells are free to grow and multiply, threatening your health.

Anti-Cancer Immune Response Steps

Immunotherapy is a revolutionary class of cancer drugs that help your body recognize and eliminate cancer. This anti-cancer immune response is initiated in a series of steps.

A cancer cell dies (this is called apoptosis) and releases cancer cell-specific antigens that are captured by dendritic cells (DCs) for processing.

Dendritic cells use major histocompatibility complex (MHC) molecules to present the cancer antigens on their cell surface.

T cells then recognize the cancer antigens, resulting in priming and activation of effector T cell response against them.

The T cells now recognize the cancer as “foreign” rather than “self.” The newly activated cytotoxic T lymphocytes (CTLs) migrate to the tumor.

CTLs infiltrate the tumor bed.

CTLs recognize and bind to cancer cells through interaction between the T cell receptor (TCR) and its equivalent antigen, presented by MHCI on the surface of the cancer cell.

The interaction of CTLs with tumor cells initiates the death of both cells. The death of those cells releases additional tumor-associated antigens (the cycle begins again at Step 1), increasing the breadth and depth of the response in subsequent revolutions of the cycle.

Today in Immunotherapy

Several types of immunotherapy are currently in clinical development, including vaccines and “adoptive immunotherapy,” which has been successful in treating hematologic malignancies. However, one of the most promising types of immunotherapy, known as checkpoint inhibitors, are already available for treating a great number of solid tumor cancer types today.

Checkpoint inhibitors stimulate a patient’s immune system to recognize cancer cells as “non-self,” prompting the immune system to attack the cancer cells. These treatments work in one of two ways: by blocking proteins on the cancer cell surface with monoclonal antibodies; or by inhibiting receptor proteins on the surface of T cells with monoclonal antibodies. Both of these mechanisms of action “uncloak” cancer cells that hide from attack by the immune system. Once the immune system can recognize a tumor, it can work to eliminate cancer cells in a similar fashion to the immune system’s response to viral or bacterial infections.

Checkpoint Inhibitor Therapy

%

of patients treated with checkpoint inhibitors respond.

The Benefits

About 30% of patients treated with checkpoint inhibitors respond, and for a small proportion of those who do, the results can be completely transformational and durable. For example, in August 2015, former U.S. President Jimmy Carter announced that he had an aggressive form of melanoma skin cancer, with metastasis to both his liver and his brain. On December 6, 2015, after he was treated with Keytruda® (pembrolizumab) from Merck & Co., all signs of his cancer were reported gone. [2] (Swetlitz, 2015). And nearly one year after his initial treatment was completed, there was still no evidence of disease

clinical trials are currently underway.

The Drawbacks

However, despite the promise of potential curative-like results from checkpoint inhibitor therapy, many patients will not respond, and some may even experience harmful adverse effects. The 70% of patients who do not ultimately benefit from these drugs – which can cost $150,000 USD or more – lose critical treatment time that could have been spent on a different effective therapy, such as chemotherapy or targeted therapy. There are also over 1,000 clinical trials underway for new immunotherapies, combination therapies, and additional indications, underscoring an urgent need for biomarker tests that identify the patients most likely to benefit.

Currently, there are several checkpoint inhibitors with approved indications for firstline or subsequent therapy in solid tumors. Today, only pembrolizumab has an associated FDA-approved companion biomarker for first line treatment of NSCLC, i.e. PD-L1 immunohistochemistry (IHC). IHC is a useful test, but only tells part of the larger story.

Seeing the Whole Story in a Tumor Biopsy

By combining the multiple tests that make up Immune Report Card®, OmniSeq® is taking a comprehensive approach to immunotherapy, getting the whole story from a tumor biopsy. This richer story encompasses the entire area around the tumor, including the tumor cells, immune cells, and other elements.