WATCH: Houston Methodist Researchers Develop Transformational Triple-Negative Breast Cancer Therapy

A multidisciplinary team at Houston Methodist Hospital is developing a personalized cancer vaccine designed to transform treatment for women with triple-negative breast cancer, one of the most aggressive and difficult-to-treat forms of the disease.

In a recent roundtable discussion, Dr. John Cooke, chair of Cardiovascular Sciences and director of the Center for RNA Therapeutics, joined oncologist Dr. Kai Sun and nanomedicine expert Francesca Taraballi, Ph.D., to outline how the institution is combining RNA technology, immunotherapy and nanomedicine to deliver a novel therapeutic approach.

Addressing an unmet need

Approximately 10% to 15% of all breast cancer cases are triple-negative, meaning the tumors lack estrogen, progesterone and HER2 receptors. Without these targets, treatment options are limited, and many patients relapse after chemotherapy.

"That's the group of patients we really need to find new therapies for," Dr. Cooke said. "Our goal is to create a neoantigen cancer vaccine to protect against recurrence and progression of the disease."

During the discussion, Dr. Sun noted that while chemotherapy induces a complete response in about half of patients, the rest remain at high risk for metastasis and mortality. Immunotherapy has shown promise, but many tumors are able to evade detection.

"What cancer vaccines do is wake up the immune system and call in the soldiers — our T cells — to recognize and attack cancer cells," Dr. Sun said.

How it works

As detailed in the video, the protocol for developing the new triple negative cancer vaccine includes the following steps:

• Houston Methodist sequences patients' tumors to identify abnormal proteins, or neoantigens.
• Those protein sequences are encoded into an mRNA vaccine
• Dr. Taraballi's nanomedicine group encapsulates the mRNA into lipid nanoparticles — "little FedEx packages," as she described — to protect the vaccine and deliver it directly into cells
• Once inside, the vaccine instructs cells to display the neoantigens, triggering an immune response that trains the body to recognize and fight residual cancer
• Combined with checkpoint inhibitors such as pembrolizumab, the vaccine has the potential to both prevent recurrence and enhance existing therapies

The investigational approach draws on Houston Methodist's unique infrastructure: GMP clean rooms, an RNA core and integrated collaboration between clinicians and scientists. Unlike many institutions that outsource production, Houston Methodist can design and manufacture personalized vaccines entirely in-house — a critical advantage given the short treatment window after surgery.

Looking ahead

Benefits of this approach may extend well beyond triple negative breast cancer patients.

"This is about developing platform, not just a single therapy," Dr. Taraballi explains. "Once we establish it for triple-negative breast cancer, it can be adapted to other difficult cancers, like pancreatic cancer or tumors resistant to immunotherapy."

Thanks to the FDA's recent approval of a phase 1 clinical trial, the team expects to enroll its first patients in late 2025. A phase 2 trial is anticipated in 2026 or early 2027.

Dr. Cooke emphasized that the initiative represents Houston Methodist's mission to translate discovery into patient care.

"We are creating something transformational for our patients with cancer," Dr. Cooke concluded. "That's what we do here at Houston Methodist, we lead medicine."

Click on the image above to view the roundtable video.