Frontiers in Medicine: Applying Immunotherapy to More Than Cancer

By Victoria Sahadevan Fossland, MD
Medical Writer

The Frontiers in Medicine series considers advances shaping the future of medicine. This post is the second of 2 examining the role of immunotherapy in medicine. To read the related Frontiers in Medicine post, go to How Immunotherapy Is Changing Cancer Treatment.

Over the last few decades, immunotherapy has proven a valuable weapon in the war against cancer, and in some cases, has enabled cures for patients with metastatic cancer.^1-3 To date, it has been used successfully in at least 15 different types of cancer and many new immunotherapy drugs are being investigated across the US.⁴

How does immunotherapy work?

There are multiple types of immunotherapy, each of which can stimulate an immune system response designed to destroy cancer cells. For example^5-8:

• Cancer vaccines teach the body to recognize cancer cells by modifying tumor cells taken from the patient. After returning these cells to the patient, the patient’s immune system learns to recognize and destroy cells similar to the modified cancer cells.
• Cytokine therapy recruits immune system proteins, such as interferons and interleukins, to trigger an immune response.
• Immune checkpoint inhibitors downregulate inhibitory pathways, allowing for T-cell activation against multiple types of cancer.
• Chimeric antigen receptor T-cells (CARTs) use patients’ own T-cells that have been engineered to target cells exclusively found in their particular type of cancer, such as leukemia.

How is immunotherapy used for diseases other than cancer?

Immunotherapy has tremendous potential because immune cells are present in every organ and have a role in many health conditions.⁷

By manipulating immune system responses, upregulating and downregulating biological pathways as needed, immunotherapy is now used to fight infections, arthritis, and autoimmune diseases, in which the immune system attacks normal cells by mistake.^3,7

For example, after organ transplantation, CARTs can be used to decrease the immune response to foreign cells, suppressing tissue rejection and fibrosis (thickening or scarring) while promoting tolerance of the transplanted organ.⁷

As mentioned in our previous Frontiers in Medicine post, immunotherapy is considered so promising that more than 70 immunotherapy drugs are being developed and more than 1000 immunotherapy clinical trials are underway across the US.⁹

What are the adverse effects of immunotherapy?

In general, the most common adverse effects of immunotherapy are similar to flu-like symptoms, and immunotherapies can be well tolerated with only mild to moderate toxicity.^8,9 Individuals receiving immunotherapy combined with other medications may experience increased adverse effects, such as the onset of diabetes or inflammatory arthritis.⁴

However, each type of immunotherapy has distinct side effects, some of which can be severe.⁵ For example, when cytokine therapy is used, multiple downstream effects on T-cells and natural killer cells can lead to capillary leakage and a sepsis-like syndrome, which is a rare but potentially life-threatening response. In extreme cases, this can result in multi-organ failure.¹⁰

As with any treatment method, managing the beneficial therapeutic effects of immunotherapy with its adverse effects is a delicate balance. In some patients, immunotherapy can cause healthy tissues to be perceived as foreign, causing inflammation within the colon, lungs, or heart.³ Steroids and even immunosuppression itself may help avoid these serious consequences.^4,10

What’s on the horizon in immunotherapy treatment?

Immunotherapy is not universally effective for all cancers or all patients. And although 10% to 30% of cancer patients have an autoimmune disease, patients with pre-existing autoimmune diseases are usually excluded from prospective clinical trials due to concerns about flare-ups of the underlying autoimmune disease.^3,5,8

As researchers continue to improve immunotherapy, they search for ways to^1,2,8,11:

• Predict which patients will respond to and benefit most from immunotherapy
• Improve the efficacy and safety of immunotherapy for individuals with autoimmune disease
• Reduce adverse effects of immunotherapy treatment through improved understanding of the mechanisms of their toxicity
• Overcome resistance to immunotherapy
• Increase our understanding of how cancer cells evade the immune system
• Identify other immune cell types within the tumor microenvironment that play important roles in disease processes, leading to additional therapeutic targets through their regulatory mechanisms
• Reduce costs

Immunotherapy presents the potential to coordinate the effects of traditional therapies, such as surgery and radiation therapy, while adapting immune system responses to be more tumor- and disease-specific, thereby achieving long-lasting, potentially curative treatment effects.

References

1. Sharma P. What is the future of immunotherapy? MD Anderson Cancer Center. March 24, 2022. Accessed October 14, 2022. https://www.mdanderson.org/cancerwise/what-is-the-future-of-immunotherapy.h00-159538167.html
2. Lesch S, Gill S. The promise and perils of immunotherapy. Blood Adv. 2021;5(18):3709-3725. doi:10.1182/bloodadvances.2021004453
3. Study tests immunotherapy in people with cancer and autoimmune diseases. National Cancer Institute. August 26, 2019. Accessed October 14, 2022. https://www.cancer.gov/news-events/cancer-currents-blog/2019/immunotherapy-cancer-autoimmune-diseases-clinical-trial
4. Immunotherapy: precision medicine in action. Johns Hopkins inHealth. Accessed October 14, 2022. https://www.hopkinsmedicine.org/inhealth/about-us/immunotherapy-precision-medicine-action-policy-brief.html
5. Immunotherapy. MD Anderson Cancer Center. Accessed October 14, 2022. https://www.mdanderson.org/treatment-options/immunotherapy.html
6. Igarashi Y, Sasada T. Cancer vaccines: toward the next breakthrough in cancer immunotherapy. J Immunol Res. 2020. https://doi.org/10.1155/2020/5825401
7. Weintraub K. Could immunotherapy treat diseases besides cancer? Scientific American. September 30, 2019. Accessed October 14, 2022. https://www.scientificamerican.com/article/could-immunotherapy-treat-diseases-besides-cancer1/
8. Rakshit S, Molina JR. Immunotherapy in patients with autoimmune disease. J Thorac Dis. 2020;12(11):7032-7038. doi:10.21037/jtd-2019-cptn-10
9. Immunotherapy for cancer treatment. Moffitt Cancer Center. Accessed October 14, 2022. https://moffitt.org/treatments/immunotherapy/
10. Kennedy LB, Salama AKS. A review of cancer immunotherapy toxicity. Ca Cancer J Clin. 2020;70:86-104. doi:10.3322/caac.21596
11. Immunotherapy to treat cancer. National Cancer Institute. Updated September 24, 2019. Accessed October 14, 2022. https://www.cancer.gov/about-cancer/treatment/types/immunotherapy

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Victoria Sahadevan Fossland, MD, is a general surgeon and medical writer of print-based, interactive learning, and multimedia projects. She writes clinical education pieces about a wide variety of diseases. Her work explains disease pathophysiology, treatment, clinical trial research details, and concerns that can arise from both physician and patient perspectives. Victoria has used her expertise in distilling medical knowledge into readily comprehensible and accessible learning solutions to write many valuable communications, learning modules, and workshops for Encompass, including the script for an award-winning video.