Can Tumor Cells Be Used To Make A Cancer Vaccine?

The Context: Immunotherapies for cancer hold a lot of promise by training immune cells called T cells to recognize and attack cancerous cells. T cells can be trained to recognize cancer antigens (proteins specific to cancer cells), but figuring out which antigens to target can require a bit of guesswork for scientists.

The Study: By turning cancer cells into ‘antigen presenting cells’ – or APCs, which show antigens to T cells to tell them what to target – scientists have figured out how to train the immune system to recognize many cancer antigens and thus kill cancer cells more effectively. The study, published in Cancer Discovery, was led by NYSCF – Robertson Stem Cell Investigator Alumnus Ravi Majeti, MD, PhD, of Stanford Medicine.

The Importance: This study opens the door for better immunotherapies – including potential cancer vaccines – that could be used to treat both blood cancers and solid tumors by waging a stronger, multi-pronged war on the disease.

“This approach could open up an entirely new therapeutic approach to treating cancer,” said Dr. Majeti, a professor of hematology, in an article from Stanford Medicine.

The team developed their approach by attempting to mimic the body’s natural immune response, in which APCs present a group of antigens to T cells, essentially giving them a directory of who to attack. If cancer cells could be turned into APCs themselves, then they’d essentially give up a bunch of identifying information to T cells, allowing them to attack cancer from multiple angles.

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

Cancer Cells Stage a Mutiny

The scientists began by turning leukemia cells in mice into APCs, then delivering them back into the mice as a vaccine.

“When we first saw the data showing clearance of the leukemia in the mice with working immune systems, we were blown away,” said Dr. Majeti. “We couldn’t believe it worked as well as it did.”

“What’s more, we showed that the immune system remembered what these cells taught them,” he continued. “When we reintroduced cancer to these mice over 100 days after the initial tumor inoculation, they still had a strong immunological response that protected them.”

“We then wondered, if this works with leukemias, will it also work with solid tumors?” Dr. Majeti posited.

The team tested the same approach using mouse fibrosarcoma, breast cancer, and bone cancer. 

“The transformation of cancer cells from solid tumors was not as efficient, but we still observed positive results,” noted Dr. Majeti.

They then tested the approach on human leukemia cells – turning them into APCs and then exposing them to immune cells from the same patient.

“We showed that reprogrammed tumor cells could lead to a durable and systemic attack on the cancer in mice and a similar response with human patient immune cells,” Dr. Majeti explained. “In the future we might be able to take out tumor cells, transform them into APCs and give them back to patients as a therapeutic cancer vaccine.”

“Ultimately, we might be able to inject RNA into patients and transform enough cells to activate the immune system against cancer without having to take cells out first,” Dr. Majeti said. “That’s science fiction at this point, but that’s the direction we are interested in going.”

Dr. Majeti will share more about his work at The NYSCF Conference (October 23-24, 2023).

Journal Article:

Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy
Miles H. Linde, Amy C. Fan, Thomas Kohnke, Aaron C. Trotman-Grant, Sarah F. Gurev, Paul Phan, Feifei Zhao, Naomi L. Haddock, Kevin A. Nuno, Eric J. Gars, Melissa Stafford, Payton L. Marshall, Christopher G. Dove, Ian L. Linde, Niklas Landberg, Lindsay P. Miller, Robbie G. Majzner, Tian Yi. Zhang, Ravindra Majeti. Cancer Discovery. 2023. DOI: https://doi.org/10.1158/2159-8290.CD-21-0502

Cover image credit: Steve Fisch