Conventional Immunotherapy

Checkpoint Inhibitor Therapy

Checkpoint inhibitors are a revolutionary class of drugs that 'release the brakes' on the immune system, allowing it to mount a strong attack against cancer. Normally, the body uses certain proteins (like PD-1, PD-L1, and CTLA-4) as 'checkpoints' to prevent the immune system from becoming too aggressive and attacking healthy cells. However, cancer cells exploit these checkpoints to evade detection.

Checkpoint inhibitors, such as PD-L1 inhibitors (pembrolizumab, nivolumab) and CTLA-4 inhibitors (ipilimumab), work by blocking these proteins, freeing the immune system to recognise and attack cancer cells. By disrupting these checkpoints, checkpoint inhibitors unleash the immune system's full potential, often leading to lasting cancer remission, especially when combined with other therapies.

How Checkpoint Inhibitor Therapy Works

PD-L1/PD-1 Inhibition

PD-L1 is expressed in tumour cells and binds to PD-1 receptors on immune cells, effectively camouflaging the tumour. PD-L1 inhibitors block this interaction, allowing the immune cells to recognise and destroy the cancer.

CTLA-4 Blockade

CTLA-4, another immune checkpoint, regulates the immune system's response to ensure it doesn't overreact. Blocking CTLA-4 (with drugs like ipilimumab) enhances the immune response, making it more aggressive against cancer.

Understanding how checkpoint inhibitors work involves appreciating how the immune system targets and destroys cancer cells. To simplify this, we use the analogy of soldiers (immune cells) being equipped for battle against an enemy (cancer cells). The following are the five critical aspects of this process:

Number of Immune Cells 

Increasing the number of immune cells, particularly natural killer cells, is crucial for mounting a strong immune response. Therapies like GC-MSF, mushroom extracts, and herbal supplements such as astragalus and reishi help boost these cell numbers.

Activity of Immune Cells 

It’s not just about having enough immune cells; their activity must also be heightened. Treatments like photodynamic therapy, electro-hyperthermia, and intravenous vitamin C can enhance immune cell activity, turning passive cells into active cancer fighters.

Tumour Penetration

The tumour microenvironment is often hostile, with barriers that prevent immune cells from reaching the cancer. By targeting this environment with treatments like angiogenesis inhibitors and hyperthermia, we can improve immune cell penetration, allowing them to reach and destroy cancer cells more effectively.

Cancer CEll Identification

Cancer cells evade detection by the immune system. Checkpoint inhibitors expose these hidden cells by blocking their PD-L1 and CTLA-4 proteins. Once identified, the immune system can attack and destroy them.

Tumour Cell Death

Once attacked, cancer cells must be prevented from repairing themselves. Treatments like PARP inhibitors stop cancer cells from recovering, ensuring their destruction through apoptosis.

The Advantages and Disadvantages of Checkpoint Inhibitor Therapy

One of the key benefits of checkpoint inhibitor therapy is its high effectiveness, particularly in cancers that have proven resistant to traditional therapies, with the potential to induce long-term remission in some patients. 

This therapy also demonstrates strong compatibility with other treatments, including chemotherapy, radiotherapy, and other forms of immunotherapy, making it a versatile option within cancer treatment regimens. Additionally, compared to traditional approaches like chemotherapy, checkpoint inhibitors tend to cause milder and less frequent side effects, which can improve the overall quality of life for patients undergoing treatment.

Despite its benefits, checkpoint inhibitor therapy has certain drawbacks. The cost of long-term treatment can be substantial, which may pose challenges for accessibility and affordability. Moreover, although side effects are generally milder, there is a risk of rare but serious autoimmune reactions. 

In such cases, the immune system may mistakenly target healthy organs, such as the thyroid, liver, or lungs, leading to potentially severe complications. These factors underscore the need for careful patient monitoring and consideration when utilising this form of immunotherapy.

Our Approach to Checkpoint Inhibitor Therapy 

At Sanctura, we thoroughly assess the characteristics of each patient’s tumour, looking for factors such as tumour mutational burden, microsatellite instability, and the expression of PD-L1 and PD-1, which determine how likely immunotherapy is to work. This personalised approach ensures that our patients receive the most effective treatment tailored to their cancer's specific needs.

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