A team of MIT researchers has developed a new approach to attacking cancer, creating a method that allows two major branches of the immune system to work together. The new technique, which is known as cancer immunotherapy, has already proved successful in tests on laboratory mice.
Previous attempts to harness the power of the human immune system to attack tumors have focused on two different strategies. Scientists either stimulate T cells to tackle cancerous cells, or attack the tumors with antibodies. However, neither technique has proved hugely successful in its own right.
The research, conducted by a team of MIT scientists, focuses on combining the two approaches, utilizing both antibodies and T cells through the use of a specially modified molecule.
Two avenues of attack
As stated, most research that seeks to harness the power of the immune system for the fight against cancer has focused on two separate strategies. The first approach involves removing T cells from the bloodstream, programming them to attack the tumor molecules, before reintroducing them into the patient's system.
The second method focuses on attacking tumors with antibodies, which are thought to bind to cancer proteins, blocking the signals that tell cancer cells to divide, while also attracting natural killer cells that work to destroy the tumor cells.
While experimenting with a signaling molecule called IL-2, the MIT team made an interesting discovery. It's thought that the molecule can be used to generate both types of immune response, but numerous clinical trials have failed to generate positive results.
During testing, the MIT team made a breakthrough, discovering that the key to making the IL-2 work lies in the timing of its delivery. Previous lab studies showed that the molecule was capable of significantly improving the effectiveness of natural killer cells in fighting cancer cells, but it proved far less efficient in the bloodstream, where the kidneys would filter out the molecule within hours – long before it had the chance to work its magic.
To combat the issue, the researchers fused the IL-2 molecule to part of an antibody molecule, allowing it to stay in a patient's bloodstream for a much longer period of time. The fused molecule was tested on mice with an aggressive form of melanoma, with the findings showing that a weekly dose of the fused IL-2, alongside antibody drugs, lead to a halting of tumor growth. Some 80-90 percent of the mice saw their tumors disappear completely, and it was found that their immune systems were able to destroy cancerous cells injected months after the initial treatment.
Harnessing T cells
The team discovered that, while the positive results of the method can be attributed to the modified, longer-lasting molecule, the IL-2 wasn't directly responsible for the improved anti-tumor response. Instead, it was the environment that they created – in combination with the antibody treatment – that allowed the T cells to attack the cancer cells more effectively.
"The antibody- driven innate response creates an environment such that when the T cells come in, they can kill the tumor," said Dane Wittrup, Professor in Chemical Engineering at MIT. "In its absence, the tumor cells establish an environment where the T cells don't work very well."
The team found that the T cells were much more successful in killing cancer cells when delivered at the same time as the IL-2 and antibody treatment, than when they were delivered on their own.
In terms of practical application of the research, it's thought that the prolonged exposure to IL-2 provided by the new technique may improve the effectiveness of existing antibody drugs. The team is continuing with its research, exploring the possibility of adding additional proteins to the antibody/IL-2 combination to further increase the efficiency of the immunotherapy treatment.
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