GRACE :: Treatments & Symptom Management
Dr West

What Is Immunotherapy, and Why Pursue It? (An Immunotherapy Primer for Patients, Pt. 1)

Share
download as a pdf file Download PDF of this page

Immunotherapy has rapidly emerged as one of the most transformative influences on cancer care since the detection of a specific target with matched molecular therapies for many cancers. Antibodies against target receptors on cancer cells, such as rituximab (Rituxan) and trastuzumab (Herceptin), or against components of the cancer growth process, such as bevacizumab (Avastin), have been integral tools in treatment regimens for at least a decade. The mechanisms of action of these therapies involve passive processes that contribute the immune function directly to the host, who is essentially a bystander in the process. In contrast, an array of novel immunotherapy agents help regulate the vigilance of a patient’s own immune system to better channel its power to actively fight a cancer. These include vaccines to help stimulate the immune system directly, as well as factors that remove the body’s natural inhibitors of the immune system.

The immune system requires a delicate balance of vigilance against threats, whether cancer or infection, and controls to ensure that it does not become excessively sensitive and attack the body’s own cells—a process that causes auto-immune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Similar to a home security system, the immune system needs to be a regulated balance in which real threats raise an alarm, but harmless incidents, such as the wind blowing or a dog jumping on the couch, do not set it off. That regulation is a complex process of many stimulatory and inhibitory factors, and one of the ways in which cancer cells can evade destruction is lulling the immune system into inhibition using some key “checkpoint inhibitors” that mislead the immune system into believing that the cancer cells are “self.” Conversely, several of the most important new advances in cancer immunotherapy, also known as immuno-oncology, work by removing these blocks on the immune system and helping to raise the level of vigilance against the threat posed by the cancer.

Interestingly, a role for the immune system in cancer has been identified for more than a century, when an 1893 report* of tumors reduced by repeat injections of a virus gave the initial proof of a principle that is still widely practiced today: the local administration of bacillus Calmette-Guerin (BCG) into the bladder of patients with superficial bladder cancer can stimulate the immune system to eradicate the cancer. While patients with some cancers, such as kidney cancer and melanoma, have been identified as potentially having spontaneous tumor shrinkage or even eradication presumably caused by a patient’s immune function, relatively nonspecific stimulants of the immune system, known as cytokines, such as interferon and interleukin-2, have been shown to improve survival modestly or, rarely, more significantly. Unfortunately, these approaches are associated with such severe side effects that they have had very limited overall utility. But we have now entered a new era in which agents that remove the braking mechanism for the immune system can provide broad activity without very challenging toxicity.

There are two main classes of immune checkpoint blockade therapies that have entered into limited use in the practice setting, along with very extensive use in clinical trials. The first approach inhibits cytotoxic T lymphocyte–associated protein-4 (CTLA-4), which is a protein expressed on the surface of “helper” T lymphocytes that suppress an immune response to cancer cells, essentially functioning as an “off switch” for the immune system. Ipilimumab (Yervoy) is an antibody to CTLA-4 that removes that braking effect and can therefore release the immune system to combat certain cancers. Ipilimumab is typically given for four treatments and has been demonstrated to significantly improve response and survival in patients with metastatic melanoma compared with other treatment options.

Figure 1: Mechanism of Action of Checkpoint Blockade Therapies: This image is from a patient education video on immunotherapies for lung cancer, developed by the Society for Immunotherapy of Cancer (SITC). To learn more about how the novel checkpoint blockade therapies work, click the image.

The second class of checkpoint blockade therapies targets programmed cell death-1 (PD-1), a receptor on host T cells, or programmed death ligand-1 (PD-L1), its partner protein on the surface of some cancer cells. Activation of these receptors also leads to an inhibitory effect on the host immune function. Conversely, antibodies that block PD-1, such as nivolumab (Opdivo) or pembrolizumab (Keytruda),both now FDA approved as treatments for metastatic melanoma skin cancer, or those that block PD-L1, such as MPDL3280A or MEDI4736, can remove that suppressive signal and thereby activate the immune system to better recognize and attack the cancer (Figure 1).

All of these mechanisms of immunotherapy have demonstrated clinical activity in a range of cancer types as single agents. In addition, clinical trials are also testing the value of some of these different strategies employed as combinations. One such combination, the CTLA-4 inhibitor ipilimumab combined with the PD-1 inhibitor nivolumab, has been shown in early clinical trials in metastatic melanoma to lead to very encouraging response rates and survival results that eclipse the efficacy of either of these approaches alone.** Combinations of immunotherapies with established treatments such as standard chemotherapy or molecularly targeted therapies are also being pursued across a spectrum of cancer types and settings.

REFERENCES
* Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. Am J Med Sci. 1893;105:487–511.
** Wolchok JD et al. Nivolumab plus ipilimumab in advanced melanoma. New Engl J Med. 2013;369:122-133.

This educational summary is intended for patients with cancer, their caregivers, and other interested non-clinicians, and is part of a broader educational platform focused on immuno-oncology, available at www.peerviewpress.com/e158

The Immunotherapy Primer for Patients is a collaboration between GRACE and PVI, PeerView Institute for Medical Education

 

 


Leave a Reply

Ask Us, Q&A
Cancer Treatments / Symptom Management Expert Content

Archives

Share
download as a pdf file Download PDF of this page

GRACE Cancer Video Library - Lung Cancer Videos

 

2015_Immunotherapy_Forum_Videos

 

2015 Acquired Resistance in Lung Cancer Patient Forum Videos

Share
download as a pdf file Download PDF of this page

Join the GRACE Faculty

Lung/Thoracic Cancer Blog
Breast Cancer Blog
Pancreatic Cancer Blog
Kidney Cancer Blog
Bladder Cancer Blog
Head/Neck Cancer Blog
Share
download as a pdf file Download PDF of this page

Subscribe to the GRACEcast Podcast on iTunes

Share
download as a pdf file Download PDF of this page

Email Newsletter icon, E-mail Newsletter icon, Email List icon, E-mail List icon

Subscribe to
GRACE Notes
   (Free Newsletter)

Other Resources

Share
download as a pdf file Download PDF of this page

ClinicalTrials.gov


Biomedical Learning Institute

peerview_institute_logo_243