Comprehensive Guide on Cancer Immunotherapy

Cancer immunotherapy is an innovative cancer treatment option that utilizes the power of our body’s immune system to fight against the disease. Unlike conventional treatments, immunotherapy empowers your own biological defenses to identify and target cancerous cells, offering a personalized cancer treatment option.

The FDA has approved cancer immunotherapy treatment for numerous cancer types.  From successful CAR T-cell therapy for acute lymphoblastic leukemia, to PD-1 checkpoint inhibitors for melanoma and non-small cell lung cancer, to therapeutic vaccines for pancreatic cancer. Thousands of clinical trials currently underway hold promise for more progress to come.

With its focus on funding transformational research in new drug development and finding novel uses for existing therapies, Gateway for Cancer Research is at the vanguard of this promising field of cancer research.

We invite you to read on and deepen your understanding of how immunotherapy is setting a new standard in cancer treatment. Explore the science, the inspiring success stories, and learn how Gateway for Cancer Research is making a difference in cancer care.

What is cancer immunotherapy?

Simply put, cancer immunotherapy enlists the power of the human immune system to fight cancer, either by stimulating its natural function, or by introducing targeted biological therapies that help restore or strengthen it.

It is a starkly different approach – instead of targeting cancer cells themselves, some immunotherapies activate immune cells in and around cancers. This groundbreaking method stimulates immune cells in and around cancerous tissues, providing a personalized and potentially less toxic alternative to conventional treatments.

Combining immunotherapy with other treatments

A one-size-fits-all approach often falls short when it comes to cancer treatment. Specifically, for cases involving aggressive or advanced-stage cancers, a multi-modal treatment strategy becomes essential, with immunotherapy being used as part of a combination of treatments with promising outcomes.

For example, we can see how immunotherapy and chemotherapy can be used to target breast cancer cells. This dual approach amplifies tumor immunogenicity and reverses tumor immunosuppression, thereby providing a more effective way to target cancer cells.

Also, immunotherapy combined with targeted therapy is emerging as an alternative to traditional methods by not only activating immune cells in and around cancers but also inhibiting specific proteins that drive tumor growth. This amplifies the immune system’s ability to recognize and eliminate cancer cells while also disrupting the cellular mechanisms that fuel the tumor. 

How Effective is Cancer Immunotherapy?

Cancer cells often evade the immune system because they originate from normal cells, making it difficult for the immune system to recognize them as foreign. Immunotherapy aims to overcome this challenge by either stimulating the immune system to work harder or by creating lab-made substances that mimic the components of the immune system

Unlike traditional treatments like chemotherapy and radiation, which directly target cancer cells, most immunotherapy aims to assist the immune system to do the fighting. This approach to treatment, combined with traditional methods, has been gaining traction in recent years due to its potential to treat various types of cancer.

However, determining the effectiveness of cancer immunotherapy is complex. Even when 15-20% of patients achieve durable results with immunotherapy, there are many other patients who do not respond to immunotherapy drugs, and we need to further invest in immunotherapy research to continue advancing treatment options.

How does the immune system fight cancer?

The human immune system is a formidable weapon against infection and disease. Leukocytes, or white blood cells, patrol the body searching for and destroying disease-causing microbes and providing general immune protection.

They seek out certain “self” proteins that all cells have on their surfaces. The immune system recognizes these proteins on normal cells and passes them by. On abnormal cells, these proteins are altered, displaying what are called tumor antigens. As a result, they are recognized as “foreign” and trigger an attack. Specialized immune cells called killer T-cells target cancer cells and prompt them to self-destruct.

The immune system does, indeed, help to prevent and slow the development of cancer. However, cancer cells develop mechanisms for undermining and evading it.

Unlike bacteria and viruses that are relatively easily recognizable as “foreign”, cancer originates in our own cells, where it can masquerade as “self.” Cancer cells can undergo genetic changes that reduce their expression of tumor antigens making them less detectable. They have surface proteins that inactivate immune cells. And they can recruit normal cells around the tumor to help suppress immune response.

In order to get around these adaptations, we often employ multiple immunotherapies at the same time. Next, we’ll cover the different types of immunotherapy for cancer, how they work, etc.

Types of Cancer Immunotherapy

Cancer treatment was once limited to surgery, chemotherapy, and radiation. However, in recent years, immunotherapy has emerged as a game-changing technology with FDA-approved therapies. These therapies, each designed to engage with the immune system in a unique way, include:

• Immune Checkpoint Inhibitors
• Immune Modulating Agents
• CAR T-Cell Therapy
• Monoclonal Antibodies
• Cancer Vaccines

The development of immunotherapy has considerably expanded the range of cancer treatments, offering new hope to cancer patients globally. Each cancer therapy is unique, and the best form of treatment varies from one patient to another, depending on the stage and type of cancer.

Immune Checkpoint Inhibitors

Our body’s immune system has built-in regulatory mechanisms, known as immune checkpoint proteins, that prevent excessive immune responses. While these regulatory mechanisms are essential for maintaining cellular balance, they can be co-opted by cancer cells to evade the immune system’s surveillance

T-cells have “brakes” on their surface called immune checkpoint proteins. When these proteins recognize specific proteins in other cells, an “off” signal tells the T-cell not to mount an immune response.

Among these, one widely studied immune checkpoint protein, PD-1, controls apoptosis, the “programmed cell death” that is part of normal development. Certain cancer cells express high levels of its partner protein, PD-L1, which turns the T-cells “off”, enabling the cancer cell to evade self-destruction. Immune checkpoint inhibitors prevent this interaction by removing these “brakes” from the immune system.

Suzanne Forrest, MD, of the Dana-Farber Cancer Institute is testing a combination of chemotherapy with checkpoint inhibitors for the treatment of rare pediatric cancers.

Immune Modulating Agents

Immune modulating agents are a class of immunotherapies that aim to help the body’s natural defense mechanisms against cancer. Unlike checkpoint inhibitors, which primarily focus on removing inhibitory signals, immune modulating agents work by amplifying stimulatory signals within the immune system. These agents interact with various components of the immune response, including T-cells, B-cells, and signaling proteins, to create an environment conducive to a more robust and targeted attack on cancer cells.

CAR T-Cell Therapy

Immunotherapy has become an emerging field in cancer treatment, and researchers have been coming up with innovative approaches that could provide better patient outcomes. One such therapy is CAR T-cell therapy, which has been approved by the FDA for the treatment of certain types of lymphomas, leukemias, and multiple myeloma. 

This form of cell-based immunotherapy is designed to harness the body’s immune system against cancer cells by modifying the patient’s own T-cells to recognize and target cancer cells. In CAR T-cell therapy, a patient’s own T-cells are collected and genetically modified in the laboratory to express a protein called CAR, then infused back into the patient, where they locate and attach to specific proteins on cancer cells where they mount a deadly immune response. 

Therapeutic or Monoclonal Antibodies

Therapeutic antibodies are drugs designed specifically to interact with and block specific molecules or mechanisms that are necessary for cancer growth; bind to proteins that cause cancer cells to self-destruct or tag cancer cells for destruction; or recruit activated T-cells into close proximity with cancer cells.

Cancer Vaccines

Therapeutic cancer vaccines are designed to strengthen the body’s natural immune function against cancer that has already developed by delaying or stopping cell growth, shrinking the tumor, preventing cancer recurrence, or eliminating cancer cells that have not been killed by other forms of treatment.

Cancer vaccines operate on a principle similar to traditional vaccines, but instead of only preventing disease, they are aimed at treating existing conditions. These vaccines introduce specific antigens into the body, which stimulate the immune system to produce specialized T-cells targeted to attack cancer cells. The goal is to train the immune system to recognize these cancer-specific antigens, thereby enabling it to identify and destroy cancer cells that may be present in the body.

In a Gateway-funded study, Jeffrey Ward, MD, PhD, of Washington University in St. Louis is developing a personalized neoantigen vaccine in combination with an immune checkpoint inhibitor for patients with small cell lung cancer.

Does Cancer Immunotherapy Cause Side Effects?

Immunotherapy can cause side effects because it works by revving up the immune system to act against cancer, which can also cause the immune system to act against healthy cells and tissues in the body.

Different people have different side effects, and the ones you have and how they make you feel will depend on how healthy you are before treatment, your type of cancer, how advanced your cancer is, and the type and dose of immunotherapy you are getting. Some side effects are common with all types of immunotherapy, such as:

• Flu-like symptoms such as fever, chills, weakness, dizziness, nausea or vomiting, muscle or joint aches, fatigue, headache, trouble breathing, low or high blood pressure.
• Skin reactions at the needle site, which include pain, swelling, soreness, redness, itchiness, and rash.
• Swelling and weight gain from retaining fluid, heart palpitations, sinus congestion, diarrhea, infection, and organ inflammation.

All cancer treatments, including immunotherapy, can cause side effects of some kind. However, it is still important to seek treatment as soon as possible since cancer won’t go away on its own, and the symptoms and gravity of the disease can get worse.

Although severe side effects are uncommon, it is important to acknowledge their existence. Examples include hepatitis, colitis, pneumonitis, severe infections, and skin reactions, depending on the treatment and type of cancer.

There are currently two Gateway-funded studies being conducted at MD Anderson Cancer Center by Ajay Sheshadri, MD, MSCI and Yinghong (Mimi) Wang, MD, PhD to help mitigate some of the more severe toxicities related to immunotherapy.

The Future of Cancer Treatment: Embracing Immunotherapy

Immunotherapy has redefined our understanding of cancer care, shifting the focus from merely attacking cancer cells to empowering the body’s own immune system to take up the fight.

However, it’s crucial to remember that early detection remains essential to increase the chances of an effective treatment. If you or a loved one are experiencing cancer symptoms, immediate medical consultation is needed in order to evaluate the current status of the patient and evaluate treatments.

As we look to the future, the role of immunotherapy in cancer treatment is only expected to grow, but this progress relies on continuous research and clinical trials. You can be a part of this transformative journey by donating to cancer research, thereby contributing to the advancement of more effective options for cancer patients worldwide. Your support can make a tangible difference in the lives of those battling this disease.