When most people think of vaccines, they think of prevention — an injection that trains the immune system to produce antibodies against infectious diseases such as measles or polio. However, cancer vaccines are different.
Rather than preventing disease, cancer vaccines are a type of immunotherapy designed to stimulate the immune system to attack cancer cells that are already present in the body. However, they have historically struggled to deliver consistent clinical benefit.
Part of the challenge lies in how cancer vaccines work. Unlike conventional chemotherapies, which act directly on tumor cells, cancer vaccines depend on mobilizing the patient’s immune system. This requires identifying optimal antigen targets, overcoming immune suppression within the tumor microenvironment, and depending on preclinical models that often fail to accurately predict human immune responses. Add in the logistical burden of personalized manufacturing, and it becomes clear why many early vaccine programs have struggled to show decisive clinical benefit.
CellxLife is bringing cancer vaccines to the forefront again with a dendritic cell–based platform that is intended to generate a stronger and more consistent anti-tumor immune response than earlier vaccine strategies. The company has also recently entered into an exclusive licensing agreement with Mayo Clinic for a novel dendritic cell vaccine that is being evaluated in two Phase 2 clinical trials in ovarian cancer — and has already shown promising results in a prior Phase 1 study.
What are cancer vaccines?
At their core, cancer vaccines are designed to teach the immune system to recognize cancer as a target. By exposing immune cells to tumor-associated antigens (TAAs), vaccines aim to provoke a targeted immune response that can seek out and destroy cancer cells and, in some cases, establish long-term immune memory.
The earliest recorded example of this principle relied on broad immune stimulation. Going back to 1891, William Coley, a New York surgeon, observed that some cancer patients experienced tumor regression following severe bacterial infections. Coley hypothesized that immune activation via the infection could drive anti-tumor responses. He developed a treatment known as Coley’s toxin, which combined heat-killed Streptococcus bacteria with Serratia Marcescens and was able to cure hundreds of patients with bone and soft-tissue sarcoma over the years. However, the approach was inconsistent and carried significant risk, with at least two documented fatalities linked to infection.
Thankfully, immunotherapy has evolved dramatically since Coley’s time, and cancer vaccines now take a far more targeted approach. Modern platforms include DNA-, RNA-, and peptide-based vaccines, as well as cell-based approaches that directly engage key immune cells.
Why dendritic cells?
Dendritic cells, in particular, are considered a hugely promising area for cancer vaccines. As the most potent antigen-presenting cells, they play a crucial role in capturing antigens and presenting them to T cells, which is essential for initiating an immune response against cancer.
“With peptide, RNA, or DNA vaccines, you inject them, they get expressed, and you’re essentially hoping that dendritic cells find those antigens and present them to generate an immune response,” Eric von Hofe, CEO of CellxLife, told DDN. In practice, that sequence can be inefficient and highly variable.
Dendritic cell vaccines remove that uncertainty. “With this approach, you actually take the dendritic cells out of the body. You collect the white blood cells from the patient, differentiate them into dendritic cells, and then pulse them ex vivo with tumour antigens — so they’re already coated with what you want the immune system to see. It’s just a much more effective way of generating a strong immune response,” he continued.
Notably, the first therapeutic cancer vaccine approved by the FDA was a dendritic cell-based therapy, Sipuleucel-T, for patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. However, while it extended the lives of prostate cancer patients by approximately four months on average, it was also very clinically intensive, and oncologists weren’t sure how to fit it into their clinical practice.
Over time, researchers have refined this approach by optimizing how dendritic cells are activated and how antigens are delivered, including the use of adjuvants and carrier systems designed to enhance antigen presentation and T cell priming.
You’re ringing the alarm bell for the immune system.
—Eric von Hofe, CellxLife
This has been key to CellxLife’s platform. “We’ve added a proprietary step that activates the dendritic cells before they’re given back to the patient,” von Hofe said. This step increases cytokine secretion, lymph node trafficking, and inflammatory signaling. “You’re ringing the alarm bell for the immune system.”
The approach has already shown encouraging results in a Phase 1 pediatric metastatic bone cancer study conducted in the 2000s, in which 62.5 percent of children with metastatic osteosarcoma treated with the dendritic cell–based therapy survived for more than 15 years. “Eighty percent of these patients don’t survive five years,” von Hofe said. “Seeing kids living five, ten years was remarkable, not to mention 15 plus years.”
The modality is expected to apply to a wide range of solid tumors, and a Phase 2 basket trial is being planned for glioblastoma, lung, pancreatic, colorectal, and cervical cancer.
A complementary ovarian cancer platform
The Mayo Clinic vaccine follows a similar approach, but with a highly defined antigen target. “In our pediatric bone cancer study, the dendritic cells were exposed to a tumor lysate. For the Mayo Clinic vaccine, they’re exposed to folate receptor alpha peptides,” von Hofe explained.
Pioneered by Keith Knutson at Mayo Clinic, the vaccine targets folate receptor alpha, a protein that is highly overexpressed in ovarian cancer. However, it also goes a step further. “One of the big issues in ovarian cancer is that patients tend to have very high levels of regulatory T cells, which are immunosuppressive,” von Hofe said.
So you’re activating the immune system against folate receptor alpha while also dialing down immune suppression. It has its own anti–immune-evasion mechanism baked into it.
—Eric von Hofe, CellxLife
To address this, Knutson’s team also pulsed the dendritic cells with the cytokine IL-15 and a p38 MAP kinase inhibitor. “That combination drives secretion of IL-17 and generates Th17 T cells, which prevent regulatory T cells from differentiating,” von Hofe noted. “So you’re activating the immune system against folate receptor alpha while also dialing down immune suppression. It has its own anti–immune-evasion mechanism baked into it.”
In an early Phase 1 study, 19 women with advanced ovarian cancer received the dendritic cell vaccine, administered intradermally every three weeks for five doses and then every three months for seven additional doses. Of the 18 patients evaluable for efficacy, seven — nearly 40 percent — remained cancer-free for at least 10 years. Historically, long-term, cancer-free survival in this population is closer to 10 percent.
The results suggest the vaccine can induce durable immune memory, enabling the immune system to recognize and respond to cancer cells long after treatment ends. Two Phase 2 trials are now underway — one in combination with Keytruda, supplied by Merck, and one as monotherapy in earlier-stage patients.
The implications could extend beyond ovarian cancer. “You see high levels of folate receptor alpha expression in breast cancer, non-small cell lung cancer, cervical cancer, and endometrial cancer,” von Hofe said. “Endometrial cancer, in particular, has some of the highest expression levels of that target. So there are a number of other cancers that could potentially be addressed with this platform.”
The future of cancer vaccines
Looking ahead, von Hofe sees cancer vaccines settling into two complementary roles in oncology. The first is as maintenance therapy, administered after surgery and chemotherapy to eliminate residual disease and reduce the risk of relapse. The second is in combination with checkpoint inhibitors, particularly in patients whose tumors lack pre-existing immune activation.
“Checkpoint inhibitors have really plateaued in terms of activity,” von Hofe said. “Across many cancers, they work well in about 30 to 40 percent of patients. But the other 60 to 70 percent may not have activated T cells in their tumors. If there are no activated T cells to begin with, taking the brakes off doesn’t do much good.”
That is where cancer vaccines could come in. “The idea is that vaccines can supply those activated, tumor-specific T cells,” von Hofe said. “Then checkpoint inhibitors can do what they’re good at — sustaining and amplifying that response. It’s a complementary relationship.”
Despite growing clinical evidence, broader adoption of cancer vaccines may still require a shift in mindset within oncology. “It’s funny working with oncologists — they’re so used to cytotoxic drugs,” von Hofe said. “You tell them something is non-toxic, and the reaction is almost, ‘Well, then it can’t be doing anything.’ That way of thinking has to change for these therapies to really be embraced.”
If ongoing trials continue to validate durable immune memory, favorable safety profiles, and synergy with existing immunotherapies, cancer vaccines may finally move from a long-promised concept to a foundational pillar of cancer care.
