Immunotherapy for Cancer vs Cancer Vaccines

by: lim ju boo, alias lin ru wu (林 如 武)

This article is a simple version on the question about Immunotherapy for Cancer vs Cancer Vaccines.  It is written for ordinary medical doctors, biomedical scientists including patients with cancers who may be interested in other therapeutic options other than chemotherapies 

I shall write a much more technical version together with my research colleague later for oncologists and research scientists involved in cancer research

There are several major types of immunotherapy drugs used to treat cancer, generally classified by how they help the immune system fight cancer cells. The primary types include immune checkpoint inhibitors, adoptive cell therapies, monoclonal antibodies, treatment vaccines, and immunomodulators. 

Examples of the main types of immunotherapies.  

1. Immune Checkpoint Inhibitors. These are the most common type of immunotherapy. They block checkpoint proteins (like PD-1/PD-L1 and CTLA-4) that prevent T cells from destroying cancer cells.  

2. Adoptive Cell Therapy (T-cell transfer): This involves removing a patient's own T cells, modifying them in a lab to better recognize and kill cancer cells (such as CAR T-cell therapy), and returning them to the body.  

3. Monoclonal Antibodies (mAbs): Laboratory-made proteins designed to bind to specific targets on cancer cells, either flagging them for destruction or stopping them from growing. 

4. Antibody-Drug Conjugates (ADCs): A type of monoclonal antibody that is linked to a chemotherapy drug, allowing it to deliver the toxin directly to the cancer cell. 

5. Oncolytic Virus Therapy: Uses genetically modified viruses to infect and destroy cancer cells. 

6. Cancer Vaccines: Therapeutic vaccines that help the immune system recognize and attack specific antigens on cancer cells. 

7. Immunomodulators (Non-specific): These generally boost the immune system, including cytokines like interleukins and interferons, which help coordinate the immune response. 

As of 2023, there were over 11 FDA-approved immune checkpoint inhibitors (ICIs) covering more than 20 cancer types, with over 70 different immunotherapy drugs in clinical pipelines. 

For instance, Pembrolizumab (brand name Keytruda) is a widely used immunotherapy medication that helps the body's immune system fight cancer by blocking the PD-1/PD-L1 pathway. It is used to treat numerous advanced cancers, including melanoma, non-small cell lung cancer (NSCLC), head and neck cancer, triple-negative breast cancer, cervical cancer, and others, often as a first-line treatment.  Key uses and indications for Pembrolizumab are, 1.  melanoma treats advanced, unresectable, or metastatic melanoma, and is used to prevent recurrence after surgery. 2. Lung Cancer (NSCLC). This is used in various stages, often as first-line treatment for metastatic disease, particularly when tumours express high levels of PD-L1. 3. Head and Neck Cancer. It is used for recurrent or metastatic squamous cell carcinoma. 4. Breast Cancer: Pembrolizumab treats high-risk early-stage and metastatic triple-negative breast cancer (TNBC). 4. Gynaecological / GI Cancers. It is used to treats cervical, endometrial, oesophageal, and gastric cancers. 5. Lymphoma / Other Solid Tumours Used for classical Hodgkin lymphoma, cutaneous squamous cell carcinoma, and

tumours with specific genetic features (MSI-H or dMMR).

Mode of action -  It is a monoclonal antibody that inhibits the PD-1 protein on immune T-cells, allowing them to better recognize and kill cancer cells. It is given intravenously (through a vein), either alone or in combination with chemotherapy. It is also  approved for a wide variety of cancer types, often regardless of the tissue of origin, provided specific biomarkers are present. Treatment decisions are made by an oncologist  based on specific biomarkers (like PD-L1 expression) and the cancer type.

When I mentioned this casually in one of my WhatsApp chat group , a specialist doctor friend in the chat group asked if we can we use pembrolizumab to stimulate the auto immunity against cancer even in healthy individual who do not have cancer instead of using cancer vaccines

My answer to him is a straight -  NO. Here are my reasons.

Using pembrolizumab (Keytruda) in healthy individuals who do not have cancer, with the goal of stimulating immunity to prevent cancer instead of using cancer vaccines, is currently not an approved or standard medical practice. While some research is exploring the concept of "immuno-prevention" for high-risk, pre-cancerous conditions, treating healthy individuals with checkpoint inhibitors like pembrolizumab poses significant, often severe, risks to overall health. This approach is not used in healthy people because of these reasons: 

1. High Risk of Severe Autoimmunity
Pembrolizumab is an "immune checkpoint inhibitor." Its mechanism involves taking the "brakes" off the immune system (blocking the PD-1 receptor) so T-cells can attack cancer cells. A healthy person’s immune system is tightly regulated to prevent it from attacking its own body. By removing these brakes, pembrolizumab causes the immune system to attack healthy cells and tissues.

Then we need to consider the side effects of immunotherapy drugs They can lead to 1. severe or life-threatening autoimmune conditions, including pneumonitis (lung inflammation), colitis (bowel inflammation), hepatitis (liver damage), nephritis (kidney damage), and damage to endocrine glands. See link:

www.keytrudahcp.com

2. "Unmasking" Autoimmunity
In healthy individuals, the PD-1/PD-L1 pathway is crucial for maintaining tolerance to self-tissues. If this pathway is blocked, the immune system may attack organs, resulting in autoimmune diseases like Type 1 diabetes, thyroid problems, or severe arthritis.

3. Different Mechanisms: Vaccines vs. Inhibitors
Cancer Vaccines: These are designed to teach the immune system to recognize specific, foreign-looking antigens on cancer cells, providing a targeted response.
Pembrolizumab: This is a broad activator of T-cells. It does not teach the immune system to recognize cancer; it simply stops the immune system from stopping itself. If there is no cancer present, it has no specific target and primarily attacks healthy tissue.

4. Current Research on Immuno-prevention
Researchers are exploring "immuno-prevention" in very specific, high-risk scenarios, such as in patients with lung nodules that have begun to change but are not yet cancer. These are not "healthy individuals" but rather individuals with pre-cancerous conditions, and these treatments are performed within strictly controlled, experimental clinical trials.

No, it is not safe or effective to use pembrolizumab as a general, preventative, "vaccine-like" measure in healthy individuals. The potential risks.  Using pembrolizumab (Keytruda) in healthy individuals who do not have cancer, with the goal of stimulating immunity to prevent cancer instead of using cancer vaccines, is currently not an approved or standard medical practice.

While some research is exploring the concept of "immuno-prevention" for high-risk, pre-cancerous conditions, treating healthy individuals with checkpoint inhibitors like pembrolizumab poses significant, often severe, risks to overall health.