At the prestigious American Association for Cancer Research (AACR) Annual Meeting 2025, researchers from The University of Texas MD Anderson Cancer Center unveiled promising results from several pioneering clinical trials that could redefine treatment paradigms across multiple cancer types. The presentations, covering personalized vaccines, metastasis-directed radiation therapy, and engineered exosome therapeutics, signal major advances in personalized oncology and immunotherapy.
Personalized Vaccine Platform for Metastatic Colorectal Cancer Shows Strong Immune Activation
In a Phase I feasibility study, a personalized vaccine platform known as NeoAg-VAX was tested on patients with microsatellite-stable metastatic colorectal cancer (MSS mCRC), a particularly challenging subtype with limited treatment options. Led by Drs. Saurav Daniel Haldar and Michael Overman, the research team used bioinformatics and sequencing technologies to create individualized vaccines targeting up to 10 tumor-specific mutations per patient.
The vaccines were administered with and without pembrolizumab immunotherapy across 28 patients. NeoAg-VAX was found to be both safe and feasible, eliciting strong immune responses in the majority of participants. Importantly, the team also analyzed the immune cell composition in patients’ tumors, providing valuable molecular insights that could guide future personalized treatment strategies.
“Lab-grown immune responses from personalized vaccines could open new doors for patients who traditionally see limited benefit from conventional immunotherapy,” Haldar explained. The results will be formally presented on April 27.
Radiotherapy Offers a Low-Toxicity Alternative for Kidney Cancer Patients
For patients with metastatic clear cell renal cell carcinoma (ccRCC), systemic therapies such as immunotherapy and tyrosine kinase inhibitors often come with significant side effects. In a prospective Phase II trial, Drs. Chad Tang and Pavlos Msaouel explored metastasis-directed radiation therapy as a less toxic alternative for 121 patients with oligometastatic ccRCC.
Results showed a median progression-free survival (PFS) of 18 months and a median systemic therapy-free survival (STFS) of 34 months, all without compromising overall survival (OS). OS rates remained high at 94% and 87% at two and three years, respectively.
Notably, the study introduced a novel circulating tumor DNA (ctDNA) assay to detect molecular residual disease (MRD). Patients who were MRD-negative had significantly longer systemic therapy-free survival (54 months) compared to MRD-positive patients (27 months), highlighting ctDNA’s potential as a powerful personalized prognostic tool.
“Our findings suggest that patients can safely defer systemic therapy and its associated toxicities without sacrificing survival,” Dr. Tang said. He will present the data on April 28.
Engineered Exosomes Offer New Hope Against KRAS G12D Pancreatic Cancer
KRAS G12D mutations, present in over 40% of pancreatic cancers, have historically resisted effective targeting by conventional therapies. In an innovative first-in-human Phase I trial, a research team led by Drs. Valerie LeBleu, Shubham Pant, Elizabeth Shpall, and Brandon Smaglo tested engineered exosomes carrying small interfering RNA (siRNA) specifically designed to silence the KRAS G12D gene.
Twelve patients with metastatic pancreatic cancer received the exosome-based therapy, and six showed stable disease with no dose-limiting toxicities. Circulating KRAS G12D DNA levels dropped following treatment, indicating target engagement. Preclinical models further suggested that combining exosome therapy with immune checkpoint inhibitors could reshape the tumor microenvironment and overcome immunosuppressive barriers.
“This work opens a new frontier in using precision exosome engineering for directly attacking genetic mutations,” Dr. LeBleu noted. The findings will be presented on April 29, and a Phase II trial combining exosomes with checkpoint blockade therapies is already planned.
Emerging Targeted Therapies Also in Spotlight
Additionally, MD Anderson researchers will share early trial results for the ATR kinase inhibitor ART0380, developed through MD Anderson’s Therapeutics Discovery division and licensed to Artios Pharma. Preclinical and translational studies published in Clinical Cancer Research have demonstrated potent antitumor activity, and investigators are refining patient selection strategies based on specific molecular tumor characteristics.
A Glimpse Into the Future of Oncology
These breakthroughs from MD Anderson reflect a broader shift toward highly individualized, less toxic cancer therapies. By tailoring treatments based on patients’ specific tumor profiles and genetic makeup, researchers aim to increase efficacy while minimizing side effects—ushering in a new era of precision medicine.
“As our understanding of tumor biology deepens, the integration of immunotherapy, genetic engineering, and biomarker-guided approaches holds tremendous promise for revolutionizing cancer treatment,” said an MD Anderson spokesperson.
With multiple trials entering Phase II and broader clinical development, the discoveries showcased at AACR 2025 signal that durable, personalized solutions to some of oncology’s toughest challenges may soon move from research labs to mainstream clinical practice.
