Harnessing The Power Of Immunotherapy For Breast Cancer

In recent decades, immunotherapy has been a game-changer in cancer treatment. Drugs that augment the body’s natural immune response against malignant tumors have dramatically improved survival rates for patients with diseases like lymphoma, lung cancer, and metastatic melanoma. But the method has been far less successful in breast cancers—particularly the most aggressive ones. Sangeetha Reddy, a physician-scientist at The University of Texas Southwestern Medical Center, is trying to change that. “We could do better,” she says.

Reddy works with patients with triple-negative breast cancers, so-called because the malignancies don’t have any of the three markers scientists have historically targeted with anti-cancer drugs. Even with aggressive chemotherapy and surgery, the prognosis for these patients—who account for about 15 percent of breast cancer diagnoses worldwide—is relatively poor. Immunotherapies, in particular, often fail because breast cancers tend to hobble the body’s dendritic cells, the roving molecular spies that sweep up pieces of suspicious material and carry them back to immune system headquarters to introduce as the new enemy. When the body doesn’t know what it’s supposed to be attacking, boosting its power is of little use.

Reddy is therefore trying to figure out how to restore dendritic cell function. As a physician-scientist, she uses a relatively new approach that she describes as “bedside to bench and back.” She treats patients in her clinic, conducts in vitro and mouse experiments in her lab, and designs and manages her own clinical trials. This physician-scientist method enables a positive feedback loop: Reddy can analyze tumors excised from her own patients to assess whether treatments are working. Then she can test out new drugs on those same cancer cells. When she identifies a promising tactic, she can design clinical trials to test things like safety, dosage, and timing. At every step, she can find something in what she learns to incorporate back into her research or her patients’ care.

This cyclical strategy has led Reddy to the combination of three drugs that she’s currently testing against triple-negative breast cancer: Flt3-ligand, a protein that stimulates the proliferation of dendritic cells; a chemical that helps activate these cells and others; and anthracycline, a standard chemotherapy agent. In mice, this triad kept breast cancer tumors at least 50% smaller than chemotherapy alone. “A couple of our mice, we actually cured them,” says Reddy. A Phase-1 clinical trial investigating the safety and efficacy of the regimen in people began enrolling patients earlier this year.

Though it can take years to work out all the kinks in a new cancer treatment and clear the hurdles on the way to FDA approval, Reddy’s multi-pronged strategy should streamline this process as much as possible. Doing so will allow her to enable a transformation she’s been eyeing since she started to specialize in cancer treatment more than eight years ago. As a fellow at the MD Anderson Cancer Center, Reddy worked with melanoma patients in clinical trials of immunotherapy, which gave her a firsthand look at the treatment’s emerging potential. “We were taking patients who would have passed away within months and giving them ten years,” she says. “Just that hope that we can get there with [triple-negative breast cancer] led me to this path.”—M.G.

Publication: Jessica Eno, et al., Immunotherapy Through the Years, NIH NLM (2023). DOI: PMC61880924

Original Story Source: University of Arizona