Cancer immunotherapy has been hailed as the most promising treatment against cancer in recent decades, but what exactly is immunotherapy? Is Immunotherapy right for me?
Immunotherapy is a type of cancer treatment that utilizes the patient’s own immune system to fight cancer. Currently, two categories of immunotherapy have been approved by the US FDA:
Many other types of cancer immunotherapy are being researched and developed such as cytokines, oncolytic virus therapy and cancer vaccine, but they have not yet been approved by the FDA.
A key feature of the immune system lies in its ability to distinguish between healthy cells (self) from abnormal cells (non-self) before attacking the abnormal cells. To avoid accidentally damaging healthy cells, the immune system has a “checkpoint” system, where normal cells can activate the “brake” of immune T cells to stop an immune attack.
Cancer cells evolved from normal cells, and cancer cells often have mutated proteins presented on their cell surface that allows immune cells to flag them as foreign. However, cancer cells can evade immune attack by mimicking normal cells to activate the "STOP" button of the T cells, which acts like a “brake” that prevents the immune cells from attacking cancer cells.
Immune checkpoint inhibitor works by turning off the checkpoint mechanism, which prevents the cancer cell from activating the brake on T cells. The T cells become activated again and start attacking the cancer cells.
Immune checkpoint inhibitors have been approved on various types of solid tumors including lung cancer, stomach cancer, liver cancer, colorectal cancer, head and neck cancer, kidney cancer, etc. Currently, many clinical trials are evaluating the role of immune checkpoint inhibitors in combination with chemotherapy or targeted therapy.
Checkpoint inhibitors may cause T cells to become overactive. Some common side effects include skin rash and flu-like symptoms. Serious side effects can occur but only in a small percentage of patients.
Checkpoint Inhibitors approved by the US FDA: (As of 2020/02)
Merck’s Keytruda grasps FDA approval again with TMB-H biomarker regardless of tumor type (2020/07/07)
In CAR T-Cell therapy, the patient’s own T cells are extracted from blood, and then genetically modified to add special receptors to the surface of the T cells. The added receptors are called Chimeric Antigen Receptor (CAR) and they help T cells recognize and attack cancer cells. Next, the modified T cells are multiplied and returned to the patient’s body. CAR-T cell therapy is a one-time treatment.
The main side effects of CAR-T cell therapy include high fevers, body aches, fatigue, and nausea. A small number of patients have developed more serious side effects such as low blood pressure and swelling in the brain that can potentially be fatal. CAR-T cell therapy has shown remarkable responses in several kinds of blood cancers, but the clinical results in solid tumor have been much less encouraging. CAR-T cell therapy is still a very new form of cancer treatment, and researchers are working hard to make it safer and effective for more types of cancers.
Immunotherapy has shown impressive and durable results on some patients who have failed multiple lines of treatment. Immunotherapy, however, is no miracle drug yet. In addition to the astronomical price and the risk of side effects, the biggest problem faced with immunotherapy is its low response rate, with only about 20% of patients responding to treatment on average.
So are there ways to tell if a patient is suitable for immunotherapy? Physicians can now predict whether checkpoint inhibitors will work on someone or not using “biomarkers.” Biomarkers are biological characteristics at DNA or protein level that can help doctors detect the presence of a disease or predict response to treatments.
For immune checkpoint inhibitors, the main predictive biomarkers are as below.
In May 2017, checkpoint inhibitor Pembrolizumab (Keytruda) was approved by FDA for all solid tumors with high microsatellite instability (MSI-High). Previously, FDA has been approving cancer therapy based on the original location of the tumor (For example, approving a drug for lung cancer). Pembrolizumab is the first cancer drug that was approved based on the presence of a tumor’s biomarker or a specific genetic feature, rather than the type of cancer.
Currently PD-L1 is the biomarker most commonly used by doctors to predict immunotherapy response, but selecting patients solely based on PD-L1 test results may be insufficient. A 2017 study shows that the response rate of patients who are both TMB-high and PD-L1-high is approximately twice as high as patients who are only TMB-high or only PD-L1-high. (N Engl J Med 2017;376:2415-26.)
PD-L1 testing can usually be ordered from your hospital or facility. The three main genomic biomarkers for checkpoint inhibitors - MSI, TMB and immune-related genes - can be evaluated using ACTOnco®+ comprehensive genomic profiling. With the high price tag and the risk of side effects, it is essential to identify patients most likely to benefit from immunotherapy.
☛ ☛ ☛ Cancer management is highly complex. In addition to genomic profiles, many factors need to be considered when making treatment decisions, such as the patient’s overall condition, treatment history and other test results. Therefore, it is essential to discuss with your doctor and have your doctor comprehensively evaluate whether immunotherapy is right for you.