An article recently published in Nature has identified a potential way to manipulate the immune system into attacking cancer cells. This therapy has the potential to be a universal class of vaccines for the treatment of cancer.
The immune system is composed of two parts, the innate and adaptive immune systems. Together these two branches work to protect the body. The innate immune system responds to the presence of an infection immediately but is relatively non-specific and responds to many different invaders of the body in a similar way. In contrast, the adaptive immune system is slower to respond but creates a much more specific response and has the ability to remember an invader, eliminating it more effectively the second time it is encountered. Some important players in the adaptive immune response are the effector T-cells. With the help of many other components of the immune system, these cells eliminate disease-causing organisms. These organisms are recognized by the body because they have specific molecules on their surface known as antigens. The immune system can recognize these antigens as foreign and initiate a response to eliminate the pathogen.
Although effector T-cells are essential in killing an invader, they cannot recognize antigens by themselves. For a T-cell to respond to an infection, it must first interact with an Antigen Presenting Cell (APC) such as a dendritic cell. These APCs show the T-cell what antigen is on the surface of the invader and tells it how to respond to the organism. When a vaccine is administered, antigens from a certain disease-causing organism are injected into a person so that the adaptive immune system can learn to recognize them. Because of this, if the actual pathogen is ever present, the immune system will already know how to respond. This system is essential for protecting the body from infectious disease but in a recent Nature publication, a group of scientists were hoping to find a way to use the same system to turn the immune system against cancer cells.
Like foreign organisms that cause disease, cancer cells also have antigens on their surface that have the potential to be recognized by the immune system. Cancer cells arise from our own cells and can be very good at hiding from the immune system. If the immune system could recognize the cells as harmful, then it could kill the cells and eliminate the tumour. The study presented here aimed to do this through design of a nucleic acid vaccine known as an RNA-lipoplex. RNA is a nucleic acid that acts as a messenger. If this message can be taken up by APCs, they can present the corresponding antigen to T-cells. Subsequently, the T-cells will be able to attack the cancer cells that carry this antigen. Previously this has been tried by simply injecting mice with the RNA message. However, RNA can easily be degraded and therefore is unable to get to the necessary location. However, this study found that by packaging the RNA in a slightly negative coating of lipids, the RNA was protected and could be targeted to the dendritic cells within the spleen, lymph nodes, and bone marrow in mice. This occurred when the vaccine was administered systemically through the blood. These locations contain a large number of dendritic cells and T-cells and therefore are optimal places for this RNA-lipoplex to elicit its effects. Ideally, following arrival of the vaccine, the dendritic cells will take up the message, relay it to the T-cells, and active T-cells that can recognize and destroy cancer cells will be released into the blood.
The study presented here looked at this system in mice and found that vaccination with an RNA-lipolex led to a number of indications that the immune system had been stimulated. They observed increased dendritic cells presenting this antigen to T-cells, increased activated T-cells, and also the increased levels of interferon alpha (IFNa), a molecule that is important in promoting the immune response. The researchers found that mice given the vaccine and then purposefully injected with tumour cells did not develop cancer. However, those that did not receive the vaccine, but were exposed to cancer cells, all died within 30 days. Furthermore, they found that when three rounds of the vaccine were administered to mice with metastatic lung cancer, the tumours were eliminated and did not return in the 20 days following the final immunization. These results indicate that the RNA-lipoplex developed here has the ability to both prevent and treat cancer in mice.
As a result of the promising findings observed in mice, a clinical trial has been initiated to test this treatment in humans. This trial is currently in phase one which means that the primary goal is to assess the safety of the vaccine. So far, the treatment has been well tolerated in three advanced melanoma patients, resulting in mild flu-like symptoms. The dose administered to these patients was below what was considered therapeutic within the mice and therefore it is difficult to estimate how effective it will actually be in treating human cancers. It is essential to establish the safety of the vaccine before efficacy can be assessed.
The form of cancer treatment developed by the authors of this article is known as immunotherapy, currently a particularly exciting branch of cancer research. Essentially what these researchers have accomplished is the ability to manipulate a patient’s own immune system into attacking a tumour the way it would an infection. At this time, the efficacy of the vaccine has only been shown in mice and as such, caution must be exerted until it can be shown to be equally effective in humans. However, if found to eliminate human cancers, this vaccine could theoretically be modified to direct the immune system to recognize any cancer type based on the antigens found on the tumour’s surface. Because of this, RNA-lipoplex vaccines have the potential to be a universal class of vaccines for the treatment of cancer.
Written By: Katrina Cristall, BSc (Hons)