Rare T Cells Fight Cancer

A new approach to immunotherapy finds that the immune-cell clonotypes that come to the rescue start out at very low frequencies.

May 1, 2017
Jef Akst

T-CELL TARGET: Metastatic melanoma, pictured here, has been in the sights of immunotherapy developers. © ISTOCK.COM/BEHOLDINGEYE

The paper
A.G. Chapuis et al., “Tracking the fate and origin of clinically relevant adoptively transferred CD8+ T cells in vivo,” Sci Immunol, 2:eaal2568, 2017.

T-cell therapy
One approach used in cancer immunotherapy is to extract T cells from a patient’s blood, select a single clonotype that binds to a tumor antigen, expand it in culture, and reintroduce the cells to the body. Reaching therapeutic levels, however, might take several months, sometimes too late to save the patient.

The solution
Rather than generating a therapeutic population of lymphocytes from a single T cell, Fred Hutchinson Cancer Research Center immuno-oncologist Aude Chapuis and her colleagues decided to infuse patients with a polyclonal group of cells stimulated by a particular tumor antigen. “Instead of picking one cell and growing it out, we’re taking a lot of cells and growing them a lot less,” on the order of just four to six weeks, Chapuis says.

The result
The researchers tested the approach in 10 metastatic melanoma patients, tracking T cells in the blood via high-throughput sequencing. They found that, not only did the cells persist, the immunodominant clones that emerged existed only in very low frequencies in the body prior to the therapy. “The results demonstrate that long-lasting T cells are derived from a very rare, extant pool of largely inexperienced and probably naive T cells,” says coauthor Cassian Yee of the MD Anderson Cancer Center.

The long view
In the two patients who had complete remissions, a single dominant clone took over. “Sometimes there’s just this perfect fit and [one T cell type] just goes to town,” says Nicholas Restifo, who studies T cell–based immunotherapies at the National Cancer Institute and was not involved the study.