In a week marked by remarkable advances in cancer immunotherapy, scientists from two leading California institutions have unveiled research that could reshape the future of cancer vaccines. With breakthroughs spanning both virus-driven and genetically driven cancers, these studies illuminate new hope for patients facing some of the world’s most stubborn malignancies.
At the Keck School of Medicine of USC, a team led by Dr. W. Martin Kast published a pioneering study on August 19, 2025, in the Journal for ImmunoTherapy of Cancer. Their work uncovers how the most dangerous strain of human papillomavirus, HPV16, manages to outwit the body’s immune defenses—an insight that could finally unlock the full potential of therapeutic vaccines for HPV-induced cancers.
HPV16 isn’t just another virus. According to USC researchers, it’s implicated in more than half of cervical cancers and a staggering 90% of HPV-related throat cancers worldwide. While preventive vaccines like Gardasil-9 have been a public health triumph, they only work if given before exposure to the virus. For the millions already infected, the race is on to develop therapeutic vaccines that can rally the immune system to hunt down cancer cells after the fact. But so far, these vaccines have achieved only modest results, leaving scientists puzzled as to why.
The new study offers a compelling answer. Using both mouse models and cultured human cells, the USC team discovered that HPV16’s notorious E6 and E7 proteins reprogram nearby macrophages—key immune cells—prompting them to secrete high levels of interleukin-23 (IL-23), a signaling molecule. The twist? IL-23, instead of boosting the immune response, actually suppresses the tumor-fighting T-cells that vaccines aim to activate. As Dr. Kast put it, "These findings disrupt the previous assumption that inflammatory signals invariably stimulate anti-tumor immunity." In this case, IL-23 creates an environment where cancer can thrive, hidden from the immune system’s watchful eye.
But there’s a silver lining. The researchers tested a combination treatment in mice: neutralizing IL-23 with antibodies while administering an experimental therapeutic vaccine. The result was dramatic—T-cells surged into the tumors, clearing them more effectively and extending survival. The study notes, "When these antibodies were administered in conjunction with an experimental therapeutic vaccine, the combination therapy dramatically enhanced T-cell infiltration and tumor clearance, leading to prolonged survival times."
This synergy is particularly exciting because IL-23 inhibitors are already FDA-approved for autoimmune diseases like psoriasis. That means, as Dr. Kast emphasized, "Leveraging these existing therapeutics could revolutionize the way HPV-related cancers, especially those resistant to current vaccine strategies, are treated in the near future." The team’s molecular sleuthing also revealed that the upregulation of IL-23 is driven by the transcription factor Kruppel-like factor 2 (KLF2), offering drug developers a new target to disrupt HPV’s immune sabotage at its source.
What’s more, the implications may reach beyond HPV. The study points out that IL-23 overexpression has been detected in other cancers, such as testicular and bladder cancers, hinting at even broader therapeutic potential. Still, the researchers urge caution, noting that "further investigation is necessary to delineate the precise role of IL-23 across different tumor microenvironments before these findings can be generalized."
While USC’s team pushes toward clinical trials with a proprietary vaccine designed to be paired with IL-23 inhibitors, another California powerhouse is making waves with a different kind of vaccine—one that could help patients with pancreatic and colorectal cancers, two of the deadliest forms of the disease.
At UCLA’s Jonsson Comprehensive Cancer Center, a clinical trial led by Dr. Zev Wainberg and his colleagues is testing an experimental vaccine called ELI-002 2P. Published August 18, 2025, in Nature Medicine, the Phase 1 trial enrolled 20 pancreatic cancer patients and five with colorectal cancer, all of whom had undergone standard treatments such as surgery and chemotherapy. What sets these cancers apart is their frequent recurrence—up to 80% of pancreatic cancers return, and the five-year survival rate hovers at a grim 13%.
The vaccine targets KRAS mutations, which drive about half of colorectal cancers and more than 90% of pancreatic cancers. These mutations have long been considered "undruggable," but the ELI-002 2P vaccine takes a novel approach. It uses lipophilic peptides—short chains of amino acids with a "tail" that sticks in the lymph nodes, where immune cells are activated. As Dr. Stephanie Dougan of Dana-Farber Cancer Institute explained, "That tail sticks in the lymph nodes where immune cells get activated. You need something to get the immune system going, and just injecting killed cancer cells or peptides doesn’t work that well."
After surgery, patients received up to six priming doses of the vaccine, with some getting boosters over six months. The results were striking: about 85% of participants mounted an immune response to KRAS mutations, and nearly two-thirds had a response robust enough to potentially prevent cancer recurrence. Even more intriguing, nearly 70% showed immune responses to other tumor cell targets not included in the vaccine—a sign that the immune system was learning to recognize a broader array of cancer threats.
Survival outcomes exceeded expectations. On average, patients survived 29 months, with recurrence-free survival stretching beyond 15 months—figures that far surpass typical outcomes for resectable cancers. Dr. Wainberg noted, "That far exceeds the rates with resectable cancers." The strongest benefits were seen in "super-responders," patients whose immune systems mounted an especially vigorous attack against the lingering cancer cells. Dr. Thomas Marron, an oncologist not involved in the study, told NewsNation, "This vaccine is about teaching patients’ immune systems how to recognize and attack those tiny amounts of cancer cells so that they keep them from coming back, increasing the likelihood that we can cure patients with surgery and chemotherapy or radiation."
Unlike many cancer vaccines that must be personalized for each patient, ELI-002 2P is "off-the-shelf," making it faster and more accessible. The team is already moving forward with a Phase 2 trial and developing an updated version, ELI-002 7P, which aims to target an even broader array of KRAS mutations.
These breakthroughs come at a time when advances in mRNA technology and gene sequencing are making cancer vaccines more feasible and affordable. As Dr. Dougan observed, "Personalized mRNA cancer vaccines are showing promise in both pancreatic and colorectal cancers, but a one-size-fits-all cancer vaccine would make treatment faster and cheaper." The trial’s results suggest it is finally possible to target KRAS mutations with nonpersonalized vaccines—something researchers long thought impossible.
Taken together, the studies from USC and UCLA signal a new era in cancer immunotherapy. By unraveling how cancers evade the immune system and developing vaccines that teach the body to hunt down hidden threats, scientists are turning the tide against diseases that have long seemed unbeatable. The road ahead will require larger trials and careful validation, but for patients and clinicians alike, these discoveries offer a rare and much-needed dose of optimism.
