Cancer is described as a rapid proliferation of mutated cells. Various mechanisms work to promote the growth and spread of cancer. Interestingly, each type of cancer is unique in its characteristics and how it ‘hides’ from the immune system. Additionally, a key hallmark includes its ability to polarize healthy immune cells to a protumor activation state that helps the tumor progress. This hallmark makes it particularly difficult to treat cancer since many of these protumor cells act as a barrier to immunotherapy.
Immunotherapy refers to cancer treatments that focus on harnessing the immune system and directing it toward the tumor. In many cases, immunotherapy activates an immune cell to recognize and target the tumor. Unfortunately, the tumor can avoid detection, which is why it is critical for scientists and physicians to find surface markers specific to tumor cells. Immunotherapies can then be developed to target these surface markers and improve cancer treatment while also reducing toxicity.
There are various forms of immunotherapies, and each are designed to target a specific aspect of the immune system. It has become common practice to combine cancer treatments to target more than one aspect of tumor development and enhance therapeutic efficacy. Recent immunotherapies have involved engineering cells to activate and more directly target tumors. One form of immunotherapy includes treatment with cytokines or proteins that activate an immune response. Cytokines are secreted and received by cells to communicate to one another. Cytokines have the ability to regulate immune responses and play a major role in disease progression. Although cytokine therapy brings exciting promise, work is needed to understand how cytokines target the tumor and how to avoid systemic effects throughout the body.
A recent article in Nature Immunology, by Dr. Darrell Irvine and others, demonstrated that engineered cytokines can localize and elicit an effective immune response. While it has previously been shown that engineered cytokines can maintain intertumoral retention, it resulted in only moderate effects. Interestingly, Irvine and others report cytokine retention with significant tumor regression. Irvine is Associate Director of the Koch Institute for Integrative Cancer Research and Professor of Biological Engineering and Materials Science and Engineering. His work focuses on developing technologies to improve the safety of cancer immunotherapy and effectively target tumor growth.
Irvine and his team used various techniques including animal models to test the potency of cytokines as an immunotherapeutic. Researchers report that a localized cytokine therapy specifically targets a cell receptor known as CD45. These cytokines target immune cells that express CD45 and allow for sustained signaling. Cytokine treatment targeting CD45 combined with cytokines that stimulate immune activation were found to eradicate tumor growth and distal lesions throughout the body. These results were found in multiple models of cancer and were tested for toxicity.
When the researchers investigated the mechanism behind tumor regression, they found that CD45-targeted cytokines enhanced the antitumor activity of immune cells. Importantly, this study clearly showed that using CD45 to anchor cytokine treatment led to the effective treatment of cancer. Overall, this seminal work by Irvine and others advances our knowledge of cytokine biology and how scientists and physicians can develop strong cytokine therapeutics without off-target effects.
