How to Transform Cancer Cells into Weapons Against Cancer

Some cities fight gangs with ex-members who educate kids and starve gangs of new recruits. Stanford Medicine researchers have done something similar with canceraltering cancer cells so that they teach the body’s immune system to fight the very cancer the cells came from.

This approach could open up an entirely new therapeutic approach to treating cancer,” said Ravi Majeti, MD, PhD, a professor of hematology and the study’s senior author. The research was published March 1 in Cancer Discovery. The lead author is Miles Linde, PhD, a former PhD student in immunology who is now at the Fred Hutchinson Cancer Institute in Seattle.

Some of the most promising cancer treatments use the patient’s own immune system to attack the cancer, often by taking the brakes off immune responses to cancer or by teaching the immune system to recognize and attack the cancer more vigorously. T cells, part of the immune system that learns to identify and attack new pathogens such as viruses, can be trained to recognize specific cancer antigens, which are proteins that generate an immune response. For instance, in CAR T-cell therapy, T cells are taken from a patient, programmed to recognize a specific cancer antigen, then returned to the patient. But there are many cancer antigens, and physicians sometimes need to guess which ones will be most potent.

A better approach would be to train T cells to recognize cancer via processes that more closely mimic the way things naturally occur in the body — like the way a vaccine teaches the immune system to recognize pathogens. T cells learn to recognize pathogens because special antigen presenting cells (APCs) gather pieces of the pathogen and show them to the T cells in a way that tells the T cells, “Here is what the pathogen looks like — go get it.” Something similar in cancer would be for APCs to gather up the many antigens that characterize a cancer cell. That way, instead of T cells being programmed to attack one or a few antigens, they are trained to recognize many cancer antigens and are more likely to wage a multipronged attack on the cancer. Now that researchers have become adept at transforming one kind of cell into another, Majeti and his colleagues had a hunch that if they turned cancer cells into a type of APC called macrophages, they would be naturally adept at teaching T cells what to attack.

We hypothesized that maybe cancer cells reprogrammed into macrophage cells could stimulate T cells because those APCs carry all the antigens of the cancer cells they came from,” said Majeti, who is also the RZ Cao Professor, assistant director of the Institute for Stem Cell Biology and Regenerative Medicine and director of the Ludwig Center for Cancer Stem Cell Research and Medicine.

The study builds on prior research from the Majeti lab showing that cells taken from patients with a type of acute leukemia could be converted into non-leukemic macrophages with many of the properties of APCs. In the current study, the researchers programmed mouse leukemia cells so that some of them could be induced to transform themselves into APCs. When they tested their cancer vaccine strategy on the mouse immune system, the mice successfully cleared the cancer. “When we first saw the data showing clearance of the leukemia in the mice with working immune systems, we were blown away,” Majeti said. “We couldn’t believe it worked as well as it did.”