The researchers found that in each patient's immune system, the cells that will have the most powerful effect against a tumor are extremely rare.
The study - published in the journal Science Immunology - is the work of a team led by researchers at the Fred Hutchinson Cancer Research Center (Fred Hutch) in Seattle, WA.
Immunotherapy is an exciting new field in the fight against cancer that uses cells from the patient's own immune system to tackle the disease. However, as in all new medical approaches, it faces immense challenges.
T cells are members of the adaptive immune system, possessing several features that make them amenable for cancer treatment.
For example, T cells react specifically to threats, replicate rapidly, and travel to distant target sites. They also have long memories, suggesting that they can maintain a therapeutic effect for many years after initial treatment.
However, while the idea of using T cells looked promising in theory, scientists now face a number of hurdles before turning it into practice. One such challenge - the focus of the new study - is how to identify a readily accessible pool of tumor-specific T cells.
Clinical effect relies on 'incredibly rare' T cells
The idea of adoptive T cell transfer is to take T cells from the patient's own blood, prime them to target and kill cancer cells, multiply them in the laboratory, and then return them to the patient.
In some specific settings, the T cells can come from a healthy donor instead.
However, there are thousands of types of T cell - each with a specific cancer-killing effect - and it has not been clear which ones are the most effective against cancer cells.
Furthermore, the challenge is heightened by the fact that the cells' anti-cancer effect change as they multiply in the laboratory; the cloned offspring are different to their parents.
Lead author Dr. Aude Chapuis, an immunotherapy researcher at Fred Hutch and an expert in adoptive T cell transfer, says: "We found that the cells in each patient's immune system that will ultimately have a clinical effect are incredibly rare."
'Barcode' method tracks T cells via receptor
Dr. Chapuis says that trying to identify which cells are leading the attack on the tumor has been like trying to see into a "black box."
However, she and her team have discovered a method based on "high throughput T cell receptor sequencing" that sheds light on the problem.
Different types of T cell have slightly different weapons for tackling cancer cells, and these weapons can be distinguished by the type of receptor on the T cell.
Adaptive Biotechnologies Corp - a spin-off from Fred Hutch - have developed a way of giving each type of T cell receptor a unique "barcode" so that the researchers can read and track all the types of receptor in an individual patient's army of T cells.
Dr. Chapuis says that with the new tracking method, they can finally follow in detail what is happening in an individual patient's adoptive T cell transfer.
The method allows them to "distinguish the cells and figure out where they came from, which ones grow in culture and which ones persist after being transferred to the patient," she explains.
In their study, the researchers used the barcode method to track thousands of immune cells following their transfer into patients.
Rare, young T cells were the most powerful against cancer
The team assessed how well 10 patients with metastatic melanoma - a disease in which skin cancer had spread to other parts of the body - responded to adoptive T cell therapy using different mixes of T cell types.
Two of the patients demonstrated complete remission. On further examination, the team found that in those cases, the T cells that led the fight against the metastatic cancer were types that were extremely rare in the patients' bodies originally.
The researchers also used the new tracking method to directly monitor the T cells in the body.
They found that the T cells that delivered the strongest anti-cancer punch tended to be younger, suggesting the effect came from the fact that younger cells are more able to replicate and survive - features likely to be important for sustaining long-term effects.
"Knowing what we've found, we can now refine the selection of the cells that we will ultimately use for adoptive T cell transfer, so that the cells persist and keep the tumors at bay longer in our patients."
Dr. Aude Chapuis
The team is now conducting two clinical trials to test how to better extract the rare but powerful T cells and multiply them before returning them to patients.
In the following video, Dr. Chapuis explains how adoptive T cell transfer fights cancer, the main challenges facing researchers developing this type of immunotherapy, and the progress of the team at Fred Hutch.