Immunotherapy Overview

For decades, doctors and researchers have conducted clinical trials to further progress in the clinical implementation of tumor immunotherapy. Former President Jimmy Carter’s success with immunotherapy for advanced melanoma and Vice President Joe Biden’s Cancer Moonshot Initiative have brought this new treatment type, as well as cancer treatments in general, into the spotlight for the general public. As a result, health care professionals may experience a spike in inquiries about this new treatment.

Several immunotherapy agents are now available for melanoma. Although surgery often remains the first line of treatment, especially for early-stage melanomas, the U.S. Food and Drug Administration (FDA) is rapidly approving new immunotherapy medications for advanced melanoma.

What is Immunotherapy?

Immunotherapy is a type of treatment that uses the body’s own immune system to recognize and kill cancer cells. Cancer cells often can fool the body into not recognizing they are dangerous. If the body can’t tell the difference between cancer cells and healthy cells, cancer cells may be able to “hide” from the immune system. To identify cancer cells as a threat and target them for destruction, immunotherapy uses substances either made by the body or in a laboratory to enhance recognition or effector function of the immune response against the cancer.

Different types of immunotherapy exist. Each works in a unique way to slow and stop the growth of cancer cells, stop cancer cells from spreading to other parts of the body and help the immune system work better overall at destroying cancer cells. Some immunotherapy treatments boost the body’s immune system while others train the immune system to attack cancer cells:

  • Checkpoint inhibitors are an important part of the immune system due to their ability to keep immune cells from attacking normal cells in the body. Checkpoints are proteins on immune cells that need to be turned on or off to start/stop an immune response. The immune system uses checkpoints to prevent itself from attacking normal cells in the body and deleted immune cells after their functions have been completed, for example following clearance of an infection. But melanoma cells sometimes hijack these checkpoints to avoid being attacked by the immune system. Checkpoint inhibitors target the checkpoint proteins, helping to restore the immune response against melanoma cells.
  • Cytokines are soluble molecules that enable immune cells to communicate with each other. Cytokines work together to make sure that the immune response is of the right strength and length of time.  Laboratory-made versions of cytokines are sometimes used to boost the immune system in people with melanoma.
  • Oncolytic viruses are viruses altered in a laboratory so that they preferentially infect and kill mainly cancer cells. Along with killing the cells directly, the viruses can also alert the immune system to attack the cancer cells.
  • Cancer vaccines are substances that stimulate the immune system to fight infection or disease. Cancer vaccines strengthen the immune system against cancer cells.
  • Nonspecific immune stimulators boost the immune system in a general way to help the immune system attack cancer cells.

Certain immunotherapies work well when given alone. Others work better in combination with additional treatment strategies.

At present, the clinical use of immunotherapy is largely restricted to the adjuvant treatment of Stage III and systemic treatment of Stage IV melanomas, although there is intense interest in evaluating immunotherapy as neoadjuvant or adjuvant therapy for all stages.

Why is Immunotherapy in Demand?

Immunotherapy has the potential to achieve durable clinical responses in some patients. In addition, an improved quality of life may also make immunotherapy an attractive choice for people who have this treatment option. Immunotherapy may be an option for patients to consider because the side effects, although prevalent, may be easier on patients compared to typical chemotherapy-related toxicities, and with appropriate attention, can be simple to manage. The side effect profile differs from other types of cancer therapeutics. Some side effects occur as a result of an overactive immune system, not the destruction of healthy cells, as often occurs with cytototoxic chemotherapy. Because not as many healthy cells are damaged with immunotherapy, some patients have reported a different range of side effects.

One limitation to immunotherapy is that it can be very effective in some patients but not in others. Researchers continue to explore why this happens to determine how to improve existing therapies and to develop new ones through clinical trials. Researchers are interested in identifying biomarkers that may be able to better predict which patients are likely to respond to which immunotherapy agents or combinations.

Several immunotherapy agents or regimens are currently approved by the FDA for the treatment of melanoma. Other novel treatments that are not yet FDA-approved may be accessible through clinical trials. Discuss the opportunity to participate in a clinical trial with your patients if they have not responded to other therapies or if you feel this may be the best treatment option for them. Provide them with multiple resources, and encourage them to become advocates for their own health by learning about and researching available clinical trials. A menu of active melanoma immunotherapy trials can be found at
www.clinicaltrials.gov.

A Long History

Overview_William_Coley.jpgCancer treatments are not discovered overnight. More than a century ago, Dr. William B. Coley worked with doctors and people with cancer to study how cancer tumors reacted to bacterial infections. His treatments for people with inoperable tumors consisted of injecting a combination of bacteria directly into the tumors. The treatment shrank the tumors and sometimes even led to a cure. Dr. Coley believed the body’s increased response to the bacteria also helped fight off the cancer.

More recently, in the 1960s, Dr. Donald Morton began experimenting with a vaccine that was intended not to prevent cancer but to stimulate the body’s immune system to attack cancer cells once they had developed. An early proponent of immunotherapy, particularly cancer vaccines, Dr. Morton was at the forefront of global cancer research and treatment, with a focus on melanoma. His work with bacillus Calmette-Guerin (BCG) for melanoma led to the approval of BCG for bladder cancer, the first successful immunotherapy against a human tumor.

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SITC Resources

12-12-2022 10:54
This is the library for the Enduring Materials from the Targets for Cancer IO: A Deep Dive, TCR based therapies webinar that was conducted on December 7, 2022 . Date of Live Event: Wednesday, Dec. 7, 2022 – 2 p.m.–4 p.m. CST Moderators: Harlan Robins, PhD – Adaptive Biotechnologies ...
11-18-2022 17:51
Cancer Immunotherapy Winter School Sign up below to get an update when applications open for Winter School 2025 Tailored to early-to-mid career scientists and clinicians in the field of cancer immunotherapy working in academic, clinical, industry and government settings, this hybrid program provides ...
11-01-2022 13:02
On October 28, 2022, leading experts from the SITC Nonmelanoma Skin Cancer Immunotherapy Guideline Expert Panel presented "Case Studies in Immunotherapy for the Treatment of Nonmelanoma Skin Cancer – SITC CPG Webinar." This high-level webinar included case studies that illustrated execution of the Clinical ...
10-04-2022 12:12
On October 3, 2022, leading experts from the SITC Nonmelanoma Skin Cancer Immunotherapy Guideline Expert Panel presented "Practical Management Pearls for Immunotherapy for the Treatment of Nonmelanoma Skin Cancer — SITC CPG Webinar." This high-level webinar was designed to teach attendees how to appraise ...
10-04-2022 12:04
Nonmelanoma skin cancers (NMSCs) are some of the most commonly diagnosed malignancies. In general, early-stage NMSCs have favorable outcomes; however, a small subset of patients develop resistant, advanced, or metastatic disease, or aggressive subtypes that are more challenging to treat successfully. ...
09-28-2022 16:04
This is the library for the Enduring Materials from the Targets for Cancer IO: A Deep Dive, iPSC derived cell therapies webinar that was conducted on September 26, 2022 . Moderators: Kalle Malmberg, MD, PhD - Oslo University Hospital Jeffrey S. Miller, MD - University of Minne ...