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How Immunotherapy Works to Treat Cancer?

Cancer is one of the most challenging diseases faced by humanity. Traditional treatments, such as chemotherapy and radiation, have made significant strides in combating cancer, but they often come with severe side effects and do not always guarantee long-term success.

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What is Immunotherapy?

Immunotherapy, also known as biologic therapy, is a type of cancer treatment that boosts the body's natural defenses to fight cancer. It employs substances made either by the body or in a laboratory to improve or restore immune system function. Unlike traditional treatments that directly target tumors, immunotherapy trains the immune system to recognize and combat cancer cells more effectively.

The Immune System and Cancer

To understand how immunotherapy works, it's essential to first grasp how the immune system functions. The immune system is a complex network of cells, tissues, and organs that work together to defend the body against harmful invaders, such as bacteria, viruses, and cancer cells. When functioning correctly, the immune system can identify and eliminate abnormal cells, including cancer cells. However, cancer cells often develop mechanisms to evade immune detection, allowing them to grow and spread unchecked.

Types of Immunotherapy

There are several types of immunotherapy, each with its unique mechanism of action. Here are the most common forms:

1. Checkpoint Inhibitors: Checkpoint inhibitors are drugs that help the immune system recognize and attack cancer cells. These drugs target specific proteins on immune cells that need to be activated (or "unchecked") for an immune response to occur. By blocking these checkpoints, checkpoint inhibitors allow immune cells to better recognize and destroy cancer cells.

Common Checkpoint Inhibitors:

PD-1/PD-L1 Inhibitors: These drugs block the interaction between the PD-1 protein on immune cells and the PD-L1 protein on cancer cells, thereby boosting the immune response against cancer cells. Examples include pembrolizumab (Keytruda) and nivolumab (Opdivo).

CTLA-4 Inhibitors: These drugs block the CTLA-4 protein on immune cells, enhancing the immune response against cancer cells. An example is ipilimumab (Yervoy).

2. CAR T-Cell Therapy

Chimeric Antigen Receptor (CAR) T-cell therapy is a personalized treatment that involves modifying a patient's T cells (a type of immune cell) to better recognize and attack cancer cells. The process involves extracting T cells from the patient, genetically engineering them in a laboratory to produce receptors called CARs, and then infusing these modified cells back into the patient. The CARs enable the T cells to specifically target and kill cancer cells.

3. Cancer Vaccines

Cancer vaccines are designed to stimulate the immune system to attack cancer cells. Unlike traditional vaccines that prevent infections, cancer vaccines are typically therapeutic, meaning they treat existing cancer. They can be made from the patient's own cells or from antigens (substances that provoke an immune response) found on cancer cells.

4. Monoclonal Antibodies

Monoclonal antibodies are laboratory-made molecules that can bind to specific targets on cancer cells. Some monoclonal antibodies mark cancer cells so that the immune system can better recognize and destroy them. Others can directly inhibit cancer cell growth or recruit other parts of the immune system to attack cancer cells.

Examples:

Rituximab (Rituxan): Targets the CD20 protein on B lymphocytes, commonly used in certain types of lymphoma.

Trastuzumab (Herceptin): Targets the HER2 protein, used in HER2-positive breast cancer.

5. Cytokines

Cytokines are proteins that play crucial roles in regulating the immune system. In immunotherapy, cytokines are used to enhance the immune response against cancer. Two main types of cytokines used in cancer treatment are interferons and interleukins.

Examples:

Interleukin-2 (IL-2): Stimulates the growth and activity of immune cells, used in treating metastatic melanoma and kidney cancer.

Interferon-alpha (IFN-alpha): Enhances the ability of immune cells to attack cancer cells, used in treating certain types of leukemia, lymphoma, and melanoma.

Mechanisms of Action

Immunotherapy works through various mechanisms to target cancer cells:

1. Enhancing Immune Recognition

Cancer cells often evade the immune system by disguising themselves as normal cells. Immunotherapy can help the immune system better recognize cancer cells by exposing hidden antigens or by blocking inhibitory signals that prevent immune cells from attacking.

2. Boosting Immune Response

Some immunotherapies work by stimulating the overall activity of the immune system. By enhancing the proliferation and activity of immune cells, these therapies can lead to a more robust attack on cancer cells.

3. Targeting Specific Cancer Cells

Certain immunotherapies are designed to specifically target cancer cells without affecting normal cells. This targeted approach minimizes damage to healthy tissues and reduces side effects.

4. Altering the Tumor Microenvironment

The tumor microenvironment consists of various cells and molecules that surround and interact with cancer cells. Some immunotherapies modify this environment to make it less conducive to cancer growth and more susceptible to immune attack.

Benefits of Immunotherapy

1. Long-lasting Protection

One of the most significant advantages of immunotherapy is its potential to provide long-lasting protection against cancer. Once the immune system is trained to recognize and attack cancer cells, it can continue to do so even after treatment has ended, reducing the risk of recurrence.

2. Fewer Side Effects

Unlike traditional treatments like chemotherapy and radiation, which can damage healthy cells and cause severe side effects, immunotherapy is generally more selective in targeting cancer cells. This selectivity often results in fewer and less severe side effects.

3. Effectiveness Against Various Cancers

Immunotherapy has shown promise in treating a wide range of cancers, including those that are difficult to treat with conventional methods. It has been particularly effective in cancers such as melanoma, lung cancer, and certain types of lymphoma.

4. Potential for Combination Therapy

Immunotherapy can be used in combination with other treatments, such as chemotherapy, radiation, and targeted therapy, to enhance overall effectiveness. Combining treatments can lead to synergistic effects, improving patient outcomes.

Challenges and Future Directions

1. Not Effective for All Patients 

While immunotherapy has shown remarkable success in many cases, it does not work for everyone. Some patients may not respond to treatment, and others may experience only partial responses. Researchers are actively studying biomarkers and other factors to predict which patients are most likely to benefit from immunotherapy.

2. Immune-related Side Effects

Although immunotherapy generally has fewer side effects than traditional treatments, it can still cause immune-related adverse effects. These side effects occur when the immune system attacks healthy tissues and can range from mild to severe. Close monitoring and prompt management are essential to address these complications.

3. High Costs

Immunotherapy can be expensive, and access to these treatments may be limited by financial constraints. Efforts are underway to reduce costs and improve accessibility, but affordability remains a significant challenge.

4. Resistance and Relapse

Some cancers may initially respond to immunotherapy but develop resistance over time. Understanding the mechanisms of resistance and finding ways to overcome them are critical areas of ongoing research.

Conclusion

Immunotherapy represents a paradigm shift in cancer treatment, offering hope to patients with various types of cancer. By harnessing the power of the immune system, immunotherapy has the potential to provide long-lasting protection, fewer side effects, and increased effectiveness against challenging cancers. For the comprehensive cancer treatment in India, American Oncology Institute is recognized as the top multi-disciplinary oncology hospital known for its expertise and advanced care.