T cells are responsible for attacking foreign invaders, but they often become inactive in the wake of cancer. Adoptive T cell therapy restores the protective T cell response.
The researchers are Prof. Dirk Busch, of the Technical University of Munich (TUM) in Germany, Prof. Chiara Bonini, of the San Raffaele Scientific Institute in Italy, and Prof. Stanley Riddell, of the Fred Hutchinson Cancer Research Center and the University of Washington.
Their work focuses on T cells, a kind of white blood cell that is responsible for certain immune responses, including attacking foreign substances.
They explain that T cell immunity provides a lifelong memory that prevents diseases from recurring. With chronic diseases, however - such as cancer - the T cells often become inactive.
In recent clinical trials, adoptive T cell therapy, in which the protective T cell response is restored, has shown promising results.
At the Annual Meeting of the American Association for the Advancement of Science (AAAS 2016) in Washington, DC, Prof. Busch and colleagues reported on the progress of their ongoing adoptive T cell therapy clinical trials, in which patients receive so-called killer immune cells that target disease-related molecules.
The researchers have developed methods of rapidly selecting specific T cell subsets for use in clinical applications, and they say they are particularly interested in central memory T cells (TCMs) because they can engraft, expand and persevere long term.
They can also be genetically engineered to express new foreign body-targeting receptors without affecting their behavior in vivo.
Promising results observed in clinical trials
Prof. Busch says that he and his team have worked on developing cell products that will stay active for a long time.
"There is a lot of scientific competition, of course, as well as growing industry interest," he says, adding:
"What we bring into the game is, first, the conviction that you have to select the right cells to generate optimal cell products for therapy, together with superior techniques to do it."
There have been several roadblocks along the way to widespread clinical use, however. Finding or creating T cells that will be most effective for each individual has been very difficult. Furthermore, avoiding side effects and "finding ways to shorten the path from bench to bedside" have been obstacles the team has had to work around.
But the first clinical trials to use engineered T cells that express "chimeric antigen receptors" that recognize an antigen have yielded very promising results, which include instances of complete remission with end-stage, blood-borne cancers.
The researchers say they have also observed promising results in clinical trials of adoptive T cell therapy in the fight against chronic infection.
Approach needs to be replicable but individualized
A further avenue of research involves successfully testing a safety mechanism in pre-clinical animal models that has already been transferred to human patients.
Prof. Busch explains that they "put a marker into the T cells, so that we can give an antibody that binds to the cells that we have engineered but no others." Then, when an antibody binds to a cell, "other immune mechanisms get activated that eliminate it."
He says they call this "antibody-mediated cell toxicity."
Their end goal is to ensure the cell products are fully understood, defined and backed up by safety mechanisms so that the same approach can be used across different patients, but on an individualized level.
Prof. Busch says he and his team "believe the more defined our cell products are, the more predictable the clinical outcome will be." Although he and his team detailed their findings at the AAAAS' Annual Meeting, their full results will be published later this year.
With around 1,600 Americans dying every day of cancer, the results of these trials will bring much-needed hope.
Medical News Today recently reported on a non-invasive saliva test that detects cancer, which is soon to be trialed in patients.