The classic treatments for cancer include chemotherapy, radiation, and surgery. These can be very effective, but doctors at Mount Sinai Hospital in New York led by Linda Hammerich, Ph.D., and Joshua Brody, M.D., explored a much more radical approach and saw that their boldness paid off. Their new cancer treatment trains the body to fight its own tumors, and as they reported Monday in Nature Medicine, it’s led to significant remissions in several human patients.
The doctors have described the treatment as turning the tumors into “cancer vaccine factories,” which train the patients’ immune system to detect and fight the tumors themselves. They tested it on 11 patients with indolent non-Hodgkin’s lymphomas, an incurable type of cancer that originates in white blood cells. Unlike preventative vaccines, this one is therapeutic, which means it doesn’t prevent cancer but treats it.
“We were whatever the thing is right between delighted and surprised — but mostly delighted,” the study’s lead author Joshua Brody, M.D., director of the Lymphoma Immunotherapy Program at Mount Sinai, tells Inverse.
Recruiting the Immune “Army”
The new therapy works by recruiting dendritic cells, a type of immune cell, into a cancerous tumor by injecting it with molecules designed to stimulate the immune system. Dendritic cells are the ones that will corral the rest of the immune system into killing a tumor.
“Dendritic cells are a very big deal, but a weirdly neglected big deal,” says Brody. He likens the immune system to an army, in which T cells — cells produced as part of the body’s immune response — are the soldiers, and dendritic cells are the generals. To harness the potential of the whole army, Brody’s team had to figure out how to provide the dendritic cells with the information they needed to send the T cells to attack tumors.
Once the dendritic cells are introduced into the tumors, they’ve been recruited into the fight. Then, the patients receive low-dose radiotherapy, which kills enough tumor cells to release antigens, proteins that the immune system can recognize and fight. Antigens are produced by most infectious diseases, triggering our bodies to produce antibodies to fight back. Usually, tumors go more or less undetected by our immune systems, since they’re just mutated versions of our own cells. But by priming the tumors with the dendritic cells, damaged tumor cells will produce antigens that the body can learn to attack.
“At the end of it, what you have is the dendritic cell that gets the antigen on it, shouting orders to the T cells, saying, ‘Go look for this antigen all over the body!’” explains Brody.
A Successful Battle
And that’s exactly what happened for some of the patients. Three of the patients went into remission, while six patients had minor regressions that lasted between three and 18 months. In the PET scan below, the level of remission is clear: “you don’t need to be a radiologist to understand it,” says Brody.
Perhaps most importantly, this therapy didn’t just work on the tumors that were injected; it also worked on tumors in other parts of the body. This suggests the immune response successfully trained the body’s T cells to treat the cancer like a disease to fight it off.
“It’s really promising, and the fact you get not only responses in treated areas, but areas outside the field [of treatment with radiation] is really significant,” Dr. Silvia Formenti, chair of radiation oncology at Weill Cornell Medicine and New York-Presbyterian, who was not involved in the study, told CNBC.
Next steps will involve combining this immunotherapy with checkpoint blockade therapy, a cancer treatment that helps T cells attack cancer even more aggressively. In the new study, this combination showed a 75-percent success rate in mice, but Brody’s team has just begun testing it in human patients with lymphoma, breast cancer, and head and neck cancers. For more information about becoming part of that clinical trial, visit the team’s clinical trial registry.
Brody, for one, is extremely optimistic about the combination of checkpoint blockade and the therapeutic vaccine therapy.
“If the benefit in our patients is as profound as the synergy in the animal models,” he says, “we expect great results.”
Abstract: Indolent non-Hodgkin’s lymphomas (iNHLs) are incurable with standard therapy and are poorly responsive to checkpoint blockade. Although lymphoma cells are efficiently killed by primed T cells, in vivo priming of anti-lymphoma T cells has been elusive. Here, we demonstrate that lymphoma cells can directly prime T cells, but in vivo immunity still requires cross-presentation. To address this, we developed an in situ vaccine (ISV), combining Flt3L, radiotherapy, and a TLR3 agonist, which recruited, antigen-loaded and activated intratumoral, cross-presenting dendritic cells (DCs). ISV induced anti-tumor CD8+ T cell responses and systemic (abscopal) cancer remission in patients with advanced stage iNHL in an ongoing trial (NCT01976585). Non-responding patients developed a population of PD1+CD8+ T cells after ISV, and murine tumors became newly responsive to PD1 blockade, prompting a follow-up trial of the combined therapy. Our data substantiate that recruiting and activating intratumoral, cross-priming DCs is achievable and critical to anti-tumor T cell responses and PD1-blockade efficacy.