I always wanted to make new medicines to treat cancer patients.
For Jennifer Guerriero, PhD, the drive to develop better cancer treatments began long before she entered a laboratory.
Her grandmother was diagnosed with breast cancer the same year Dr. Guerriero was born. Growing up, she watched her grandmother live with and survive the disease — and found herself asking a deceptively simple question.
“I just remember thinking as a child, why can’t she take a pill? Why can’t she take Tylenol and her breast cancer go away?” Dr. Guerriero recalled.
Today, as an assistant professor at Brigham and Women’s Hospital in Boston, Dr. Guerriero is pursuing that goal by investigating an entirely new way to help the immune system fight cancer.
And with a recently awarded Cancer Research Institute (CRI) Lloyd J. Old STAR award, she is ready to take that idea further.
Changing the Environment Around Cancer
Immunotherapies have transformed cancer treatment by helping immune cells recognize and attack tumors. But they do not work for everyone.
One reason may lie not with the cancer-fighting T cells themselves, but with the environment surrounding the tumor.
Many tumors contain large numbers of immune cells called tumor-associated macrophages, or TAMs. Rather than helping the immune system attack cancer, some of these macrophages can suppress immune responses, prevent T cells from entering tumors, and contribute to resistance to immunotherapy.
Dr. Guerriero’s laboratory has identified a group of these macrophages that express a molecule called TREM2. Because these cells are found across many solid tumors but are largely absent from normal tissues, they may offer a way to selectively dismantle some of the defenses tumors build around themselves.
Her approach turns another type of immune cell — the monocyte — against them.
Monocytes naturally travel into tumors. Dr. Guerriero and her team are engineering a patient’s own monocytes with a chimeric antigen receptor, or CAR, designed to recognize and eliminate TREM2-positive macrophages.
The concept borrows from the engineering behind CAR T-cell therapy, but with an important difference. Instead of engineering immune cells to attack cancer cells directly, Dr. Guerriero wants to remove the suppressive cells standing in the way.
By clearing those macrophages, the hope is that T cells can better enter the tumor, become activated, and attack cancer.
Early studies in mice have already shown promising results, including tumor shrinkage, improved survival, and stronger T-cell activation. With STAR funding, Dr. Guerriero plans to investigate the safety and effectiveness of the approach, further improve the engineered cells, and work toward developing a clinical-grade product that could ultimately be tested in patients.
A Risk Worth Taking
STAR stands for Scientists Taking Risks — and Dr. Guerriero’s project captures exactly what that means.
“This is a brand-new, first-in-class therapy,” she said.
That novelty also makes the research difficult to fund through traditional mechanisms.
“I don’t think I could get it funded because this is really a first-in-class,” Dr. Guerriero said. Her laboratory already has preliminary data and momentum behind the approach, but moving quickly requires the kind of substantial investment that can be difficult to secure for an unproven idea.
For Dr. Guerriero, STAR funding means being able to expand her research program when the science is ready to move. It can help her hire new members of her team, purchase the materials needed to advance the work, and build collaborations beyond her own institution.
It also gives her something equally valuable: the freedom to pursue an idea that may not fit neatly within conventional funding structures.
“It is absolutely critical that foundations and incredible institutes like CRI can step up to fund these projects that may have the potential to lead to the next breakthrough for immunotherapy,” she said.
Investing in the Scientist Behind the Science
Although Dr. Guerriero’s own path to cancer research began with breast cancer, the implications of her work could extend much further. The suppressive macrophages her laboratory is studying are found across multiple solid tumors, raising the possibility that this strategy could eventually have applications beyond any single cancer type.
That potential is part of what makes investing in scientists at pivotal moments in their careers so important.
“I think investing in early- to mid-stage scientists and physicians is critical,” Dr. Guerriero said. “It’s going to keep the field moving forward. It’s going to help launch the next breakthrough.”
For a scientist who once wondered why there couldn’t simply be a better medicine for her grandmother, that possibility remains a powerful motivation.
By engineering immune cells to dismantle the defenses tumors use to protect themselves, Dr. Guerriero is exploring a fundamentally different way to overcome resistance to immunotherapy.
It is ambitious. It is unproven. And it is precisely the kind of idea the CRI STAR program was created to make possible.
