How Immunotherapy Treats Cancer?

10 January,2025

Immunotherapy, a word that has gained popularity in recent years, has been used longer than you imagined. In 1891, William B. Coley pioneered one of the earliest forms of immunotherapy by injecting streptococcal bacteria into a cancer patient, successfully shrinking the tumor. Over the next four decades, he treated over 1,000 patients with bacterial products known as Coley's Toxins, reporting significant success, especially in sarcomas. Despite his promising results, skepticism from the medical community and the rise of radiation and chemotherapy led to the decline of his methods. Today, Coley is recognized as the "Father of Immunotherapy," with modern science validating his groundbreaking idea that enhancing the immune system can combat cancer.

This blog explores immunotherapy in detail, from the cancers it treats to its benefits and risks. Let's learn more about the latest advancements in immunotherapy and whether it's right for you.

What is Immunotherapy? How Does it Work?

Immunotherapy is an FDA-approved cancer treatment that helps the immune system fight cancer. The immune system is your body's defense system, made up of white blood cells (WBCs), tissues, and organs that work together to protect you from infections and diseases. It can also help protect you from cancer. The immune system works by identifying substances in your body. If something doesn't belong, like germs or cancer cells, it sees them as "foreign" and attacks them. However, cancer cells are tricky because they start as normal cells that change and grow out of control. This makes it hard for the immune system to always recognize them as a threat.

Sometimes, the immune system doesn't attack cancer because the cells look too much like normal ones. Other times, the immune system tries but isn't strong enough, or the cancer cells produce substances to block the attack. Immunotherapy helps by giving the immune system extra support to recognize and attack cancer cells more effectively. It's a type of treatment that uses living substances to help the body fight cancer on its own.

How is Immunotherapy Administered? 

Immunotherapy can be delivered in different ways depending on the type of drug and the patient's needs. Here's how it is typically given:

• Intravenous (IV) Infusion: It is the most common method, where medications are delivered directly into a vein. Treatment may occur daily, weekly, monthly, or in cycles, including rest periods. The duration of treatment depends on factors such as the type and stage of cancer, the specific drug used, and the patient's response to the treatment.
• Oral Administration: Medications, such as lenalidomide or thalidomide, are taken by mouth as capsules or pills.
• Subcutaneous Injection: This method involves administering medications via an injection under the skin.
• Intravesical Administration: Medications are delivered directly into the bladder, as seen with BCG therapy.
• Topical Application: Creams or lotions are applied to the skin to treat certain skin cancers.
• Targeted Injections: Some drugs, like T-VEC, are directly injected into melanoma lesions for targeted treatment.

Intravenous and Injection Procedures 

If immunotherapy is delivered into a vein, it can be done through:

• Cannula: A small tube placed in a vein in the hand or arm.
• Central Line: A tube placed under the chest skin into a nearby vein.
• PICC Line: A flexible tube inserted into a vein in the arm and threaded into a vein in the chest.
• Portacath: A small disc placed under the skin, connected to a vein in the chest.

Treatment Process for Administering Immunotherapy

Patients often visit a clinic or day unit as outpatients. Depending on the medication, drugs may be given via pump, with the dose controlled over 10 minutes to several hours. The nurse will guide patients through the treatment schedule and procedure for each session.

What are the Different Types of Immunotherapy?

There are different types of immunotherapies. They target cancer by stimulating the immune system or enhancing its ability to recognize and attack cancer cells. Each immunotherapy type has specific mechanisms and applications depending on the cancer being treated.

Checkpoint Inhibitors

Checkpoint inhibitors are drugs designed to interfere with the immune system's natural "off switches," which cancer cells often exploit to avoid detection. 

• Normally, T cells in the immune system use checkpoint proteins like PD-1 and CTLA-4 to prevent them from attacking normal cells excessively. However, cancer cells can produce proteins like PD-L1 that bind to PD-1 on T cells, effectively camouflaging themselves and escaping immune attack. 
• Checkpoint inhibitors (nivolumab and pembrolizumab) block PD-1 or PD-L1, allowing T cells to continue attacking cancer cells. Similarly, ipilimumab blocks CTLA-4, enhancing T-cell activation and proliferation. 
• These therapies are often used for advanced cancers like non-small cell lung cancer, melanoma, and kidney cancer. Oncologists can combine checkpoint inhibitors with other treatments like chemotherapy to improve outcomes.

Adoptive Cell Therapy (ACT)

Adoptive cell therapy is a personalized immunotherapy approach in which a patient's immune cells are collected and modified in a laboratory. They are then reintroduced into the body to target cancer better. The two main types are:

• Chimeric Antigen Receptor T-cell Therapy: CAR T-cell therapy involves genetically engineering T cells to express special receptors (CARs) that can recognize specific proteins on cancer cells. Once reinfused, these T cells are better equipped to target and kill cancer cells. CAR T-cell therapy is primarily used for blood cancers such as leukemia and lymphoma, though research is expanding its application to solid tumors.
• Tumor-Infiltrating Lymphocyte (TIL) Therapy: In this approach, T cells naturally present within a tumor are harvested and multiplied in a lab. These improved T cells are then infused back into the patient, where they can effectively fight the tumor. While still experimental, TIL therapy is being investigated for cancers like melanoma and cervical cancer.

Emerging ACT technologies include CAR natural killer (NK) cell therapy, which utilizes NK cells from sources like umbilical cord blood and enhances their ability to detect and destroy cancer cells. Endogenous T cell (ETC) therapy involves selecting and expanding specific cancer-fighting T cells from a patient's blood.

Monoclonal Antibody Therapy

Monoclonal antibodies are laboratory-made proteins designed to bind to specific targets on cancer cells or within the tumor environment. These therapies work in several ways:

• Direct Targeting: Antibodies like rituximab bind to cancer cell proteins, marking the cells for destruction by the immune system.
• Conjugated Antibodies: These antibodies directly deliver toxins, drugs, or radiation to cancer cells. For example, brentuximab vedotin combines an antibody with chemotherapy, targeting lymphoma cells.
• Immune System Enhancement: Some monoclonal antibodies, such as trastuzumab, block growth signals or prevent blood vessel formation in tumors.

Radioimmunotherapy, like ibritumomab, uses monoclonal antibodies linked to radioactive substances to deliver targeted radiation to cancer cells. Monoclonal antibody therapies are commonly used for cancers like breast cancer, colorectal cancer, and lymphoma.

Cancer Vaccines

Cancer vaccines activate the immune system to recognize and fight cancer cells. Preventive vaccines, such as those for human papillomavirus (HPV) and hepatitis B virus (HBV), reduce the risk of virus-associated cancers like cervical and liver cancer. Therapeutic cancer vaccines, like sipuleucel-T for prostate cancer, are designed to activate the immune system against existing cancer. These vaccines often use tumor-specific antigens, sometimes sourced directly from the patient's cancer, to train the immune system to target the tumor more effectively.

Immune System Modulators

Immune system modulators are therapies that enhance the general activity of the immune system rather than targeting cancer cells directly. Key examples include:

• Cytokines: Proteins like interleukins (e.g., IL-2) and interferons (e.g., IFN-alpha) boost immune cell activity and communication. IL-2 helps increase T and B cells, while interferons slow cancer growth and enhance immune responses. These are used in cancers like melanoma and kidney cancer.
• BCG (Bacillus Calmette-Guérin): This modified bacterium is used to treat early-stage bladder cancer by triggering an inflammatory immune response in the bladder lining, helping to destroy cancer cells.
• Immunomodulatory Drugs: Drugs like thalidomide, lenalidomide, and pomalidomide boost the immune response and prevent tumors from growing by blocking the formation of new blood vessels. These are particularly useful in treating multiple myeloma.

Non-Specific Immunotherapies

These therapies include agents that enhance the immune system's overall capacity to fight cancer. Examples include toll-like receptor agonists (which stimulate immune cells to recognize and attack tumors) and granulocyte-macrophage colony-stimulating factors (which encourage the production of white blood cells that help combat cancer and infections).

Which Cancers Are Treated With Immunotherapy?

Common cancers treated with different types of immunotherapies are:

• Checkpoint Inhibitors: Bladder cancer, cervical cancer, esophageal cancer, head and neck cancer., hepatocellular carcinoma, high-risk triple-negative breast cancer, kidney cancer, melanoma, mesothelioma, non-small cell lung cancer.
• CAR T-cell Therapy: Blood cancers (leukemia, lymphoma, and multiple myeloma).
• Monoclonal Antibody Therapy: Bladder cancer, breast cancer, colorectal cancer, lymphomas (non-Hodgkin lymphoma, cutaneous t-cell lymphoma, and b-cell lymphoma, leukemia (hairy cell leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloid leukemia), multiple myeloma, non-small cell lung cancer.
• Cancer vaccines: Anal cancer, throat cancer, penile cancer, liver cancer.
• Immune System Modulators: Melanoma, kidney cancer, multiple myeloma, bladder cancer.

What are the Benefits of Immunotherapy?

Immunotherapy offers numerous benefits that make it a compelling option for cancer treatment. These benefits address the challenges posed by traditional therapies, enhance treatment outcomes, and improve the quality of life for many patients. Here's an in-depth look at the advantages:

• Works When Other Treatments Fail: Immunotherapy can be effective against cancers that do not respond well to conventional treatments like chemotherapy or radiation. Certain skin cancers that resist traditional methods have shown remarkable responses to immunotherapy. Immunotherapy offers new hope for patients whose cancers were previously considered untreatable.
• Enhances the Effectiveness of Other Cancer Treatments: Immunotherapy often works synergistically with treatments like chemotherapy and radiation, amplifying their effectiveness. When combined, these therapies can create a stronger and more comprehensive attack on cancer cells, leading to better treatment outcomes for cancers such as lung, bladder, and breast cancer.
• Reduces the Risk of Cancer Recurrence: One of the unique advantages of immunotherapy is its ability to train the immune system to remember and recognize cancer cells, a phenomenon called immunological memory. This reduces the likelihood of cancer returning, potentially keeping patients cancer-free for longer.
• Effective Against a Wide Range of Cancers: Immunotherapy has proven successful in treating various cancers, including lung, head and neck, bladder, kidney, and Hodgkin lymphoma. This versatility makes it a promising option for patients with different types of malignancies.
• Fewer Side Effects Compared to Traditional Treatments: Unlike chemotherapy and radiation, which often damage healthy cells and cause severe side effects, immunotherapy is more precise. It primarily targets cancer cells, leaving healthy cells unharmed. Side effects are typically mild, resembling flu-like symptoms such as fever, fatigue, or chills, making the treatment more tolerable for patients.
• Targets Individual Cell Mutations: Immunotherapy can be personalized to the unique mutations in a patient's cancer cells. This tailored approach enables a precise immune response, effectively attacking cancer cells while sparing normal tissues. Techniques like anti-cancer vaccines further enhance this specificity by using samples from the patient's tumor.
• Effective Against Resistant Cancers: Cancer cells often develop resistance to traditional therapies over time, rendering them ineffective. Immunotherapy provides a new treatment strategy that can overcome this resistance. By targeting cancer cells in novel ways, immunotherapy offers hope for patients with resistant or previously incurable cancers.
• Destroys Cancer Stem Cells: Tumors contain cancer stem cells, which are highly resistant to traditional treatments and can regenerate tumors, leading to recurrence. Immunotherapy has shown significant success in targeting and destroying these stem cells, reducing the chances of new tumor formation and improving the likelihood of long-term remission.
• Stimulates the Body's Natural Immune Response: Immunotherapy leverages the body's natural defense mechanisms, enhancing the activity of lymphocytes and natural killer cells. This systemic immune response can treat metastasizing cancers by targeting tumors that have spread throughout the body.
• Reduces the Risk of Organ Damage: Traditional cancer treatments, such as whole-body radiation and high-dose chemotherapy, often cause damage to healthy cells, tissues, and organs. Immunotherapy, with its targeted mechanism, minimizes this risk, preserving organ function and improving patients' overall quality of life.

What are the Risks of Immunotherapy?

Immunotherapy, while promising as a treatment for cancer and certain autoimmune diseases, comes with potential side effects ranging from mild to severe. Understanding these effects is essential for patients and healthcare providers to manage treatment effectively. Here are some common side effects of immunotherapy:

• Skin Reactions: Skin reactions are the most frequently reported side effects of immunotherapy. They often manifest as rashes, redness, itchiness, pain, swelling, or soreness, particularly at the injection site.
• Gastrointestinal Issues: Patients may experience diarrhea, colitis, abdominal pain, and, in severe cases, black or bloody stools.
• Flu-Like Symptoms: Symptoms such as fever, chills, fatigue, and muscle aches are common, mimicking those of a viral infection.
• Respiratory Problems: Some patients may develop coughing or experience difficulty breathing, which could indicate lung inflammation or other issues.
• Endocrine Disorders: These include hypothyroidism, hyperthyroidism, or adrenal insufficiency, which can cause symptoms like dizziness, severe fatigue, weight changes, faster heartbeat, increased hunger or thirst, and hair loss.
• Musculoskeletal Issues: Some patients report pain and weakness in joints and muscles, often due to inflammation.
• Cardiac Issues: Targeted therapies can sometimes lead to heart damage, including myocarditis (heart inflammation).
• Allergic Reactions: Severe or fatal allergic reactions to immunotherapy drugs can occur.

Severe Side Effects of Immunotherapy

• Inflammation-Related Issues: These include myocarditis (heart), pneumonitis (lungs), hepatitis (liver), and encephalitis (brain).
• Neurological Complications: Rare but serious effects can develop, such as meningitis or encephalitis.
• Autoimmune Reactions: In some cases, immunotherapy can cause the immune system to strike healthy organs, leading to conditions like type 1 diabetes or severe arthritis.
• Organ Damage: Overactive immune responses can harm vital organs, including the liver, lungs, heart, and kidneys.

Why Does Immunotherapy Cause Side Effects?

Immunotherapy strengthens the immune system to target disease-causing cells. However, this supercharged response may mistakenly attack healthy cells, resulting in side effects. While most of the side effects are mild and manageable, the risk of severe complications necessitates careful monitoring during treatment.

Unique Challenges of Immunotherapy

• Delayed Onset of Benefits: Unlike some treatments, immunotherapy may take longer to show results, requiring patience and persistence from patients and care teams.
• Variable Effectiveness: Immunotherapy does not work for everyone, with less than half of the treated individuals showing a significant response. For some, it may only slow tumor growth or provide partial symptom relief.
• Potential for Resistance: Over time, cancer cells may adapt and become resistant to immunotherapy, necessitating changes in treatment strategy.
• Mild to Severe Side Effects: While most effects are manageable, the potential for serious complications, such as organ inflammation or autoimmune reactions, underscores the importance of personalized care and regular medical follow-up.

Interesting Facts Related to Immunotherapy

• Immunotherapy was the first treatment to improve survival rate in patients with advanced melanoma, a groundbreaking achievement in oncology.
• The anti-PD-1 drug pembrolizumab became the first cancer treatment to receive FDA approval without organ-specific restrictions. It is the only cancer treatment that can be prescribed to anyone with genetically unstable metastatic cancer.
• Currently, five different classes of immunotherapies are available, which are used to treat more than 20 types of cancer.
• The human body produces 100 billion immune cells daily in the bone marrow, underscoring the immune system's remarkable capacity to replenish and maintain its defenses.
• Macrophages, often called the "big eaters" of the immune system, play a pivotal role by engulfing and destroying cancer cells, bacteria, and other harmful substances.
• B cells can make trillions of unique antibodies, enabling highly precise targeting of specific cancer cells without harming healthy tissue.
• Viruses can cause certain types of cancer, but fascinatingly, scientists can reprogram viruses and bacteria to act as tools for targeting and eliminating cancer cells.
• Vaccines can prevent diseases and help people with cancer by improving the immune system's capacity to recognize and attack malignant cells.
• Thanks to its memory function, the immune system has an incredible capacity to "remember" cancer cells, which can provide long-term protection and reduce the risk of recurrence.

To Conclude

Immunotherapy is a cancer treatment that helps your body's immune system fight cancer cells. It works in different ways, like teaching your immune system to recognize cancer cells better or blocking signals that help cancer cells hide. Immunotherapy has very few side effects compared to other treatments like chemotherapy and can even work when other treatments have stopped helping. While immunotherapy isn't right for everyone, it's a promising new approach that's giving many people with cancer hope for better outcomes.