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Cancer vaccines are a kind of immunotherapy that are meant to recognize cancer cells in the body and destroy them. But what if they could prevent the spread of cancer altogether? Well, that’s precisely what OvarianVax, the world’s first ovarian cancer prevention vaccine, strives to do.
Researchers at the University of Oxford have designed OvarianVax to train the immune system to detect and get rid of cells that are prone to developing into ovarian cancer. There were more than 324,603 new cases of ovarian cancer in 2022, according to a report by the World Cancer Research Fund International, and the rates are only rising.
As signs and symptoms of ovarian cancer do not present until later, many people with ovarian cancer are diagnosed at a late stage, making it one of the hardest cancers to treat. Preventing the development of these cancer cells would be life-saving for people who are at a high risk of developing the disease.
“Teaching the immune system to recognize the very early signs of cancer is a tough challenge. But we now have highly sophisticated tools which give us real insights into how the immune system recognizes ovarian cancer,” said Ahmed Ahmed, director of the Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine at the University of Oxford and lead for the OvarianVax project, in a press release.
OvarianVax: first ovarian cancer prevention vaccine awarded funding
The focus of OvarianVax at the moment is on people who have a BRCA1/2 gene mutation. Around half of the women who inherit this mutation will develop ovarian cancer, according to a report by the National Cancer Institute. So, a vaccine like OvarianVax could massively cut this risk.
“We need better strategies to prevent ovarian cancer. Currently, women with BRCA1/2 mutations, who are at very high risk, are offered surgery, which prevents cancer but robs them of the chance to have children afterwards. At the same time, many other cases of ovarian cancer aren’t picked up until they are in a much later stage,” said Ahmed.
To develop the vaccine, the researchers will be awarded £600,000 ($750,426) over the next three years to back preclinical studies. If successful, it will hit the clinic to be tested on high-risk people.
“Projects like OvarianVax are a really important step forward into an exciting future, where cancer is much more preventable. This funding will power crucial discoveries in the lab which will realize our ambitions to improve ovarian cancer survival,” said Michelle Mitchell, chief executive officer of Cancer Research UK. “OvarianVax builds on the exciting developments in vaccine technology during the pandemic. This is one of many projects which we hope will give women longer, better lives, free from the fear of cancer.”
In the long run, researchers aim to test the vaccine candidate more widely, across all those who are at a heightened risk of ovarian cancer.
BioNTech’s mRNA vaccine causes antitumor effects but also side effects
While the development of the world’s first prevention vaccine for ovarian cancer is a significant milestone, vaccine candidates to treat ovarian cancer are making progress across the globe. German multinational BioNTech has created the CAR-T cell-mRNA combination vaccine BNT211 for solid tumors like ovarian cancer. The CAR-T cell therapy targets the Claudin-6 antigen – highly expressed in several cancers. The RNA vaccine is designed to amplify the effect of the CAR-T cell therapy and induce a powerful immune response to destroy tumors.
BNT211 was born from a “side-effect” of the COVID-19 pandemic. A recent study revealed that COVID-19 vaccines had an unexpected benefit in people with cancer. It boosted cancer immunotherapy efficacy where 57.2% of people who received the Moderna or Pfizer-BioNTech’s shot within 100 days of starting treatment with a checkpoint inhibitor for solid tumors, were still alive three years later, compared to the 30.7% who hadn’t received the COVID-19 jab in 100 days. Although much more research is needed, this data reveals that these vaccines could slow cancer development in solid tumors, including ovarian cancer.
“Our goal is to unlock the potential of CAR-T for solid tumors and to help improve the outcomes for a broad range of hard-to-treat tumors,” Özlem Türeci, co-founder and chief medical officer of BioNTech, had said in a press release last year. “BNT211 aims to address two of the key limitations of CAR-T cell approaches in solid tumors, namely the lack of suitable cancer-specific cell surface targets and the limited persistence of CAR-T cells. To address this challenge, we have designed a CLDN6-specific autologous CAR-T cell therapy that we combine with our mRNA-based vaccine CARVac.”
A phase 1/2 trial showed a 45% overall response rate (ORR) and a disease control rate (DCR) of 74%. Out of 27 patients who were given dose level two, three had partial responses with an ORR of 59% and a DCR of 95%. However, side effects stirred unease.
More than half of the patients developed cytokine release syndromes (CRS) as a result of the treatment. CRS is a condition that occurs when the immune system releases too many cytokines into the bloodstream, spurring a severe inflammatory response. It is the most common side effect of CAR-T therapy and can be fatal if it’s not treated in time. The biotech company said at the European Society for Medical Oncology Congress that mitigating these side effects is a top priority.
Genetic vaccines make progress: TK-001 and Elenagen in the clinic
Meanwhile, in Europe, Italian biotech Takis’ TK-001 is a cancer vaccine in the clinic to treat ovarian cancer, among other solid tumors. It is another genetic vaccine – a vaccine that contains DNA or RNA – and is delivered via vectors – both adeno and plasmid DNA. It has been found to be safe so far.
DNA vaccines have captured attention lately. Massachusetts-based Curelab Oncology’s Elenagen targets the deadliest form of ovarian cancer. It is designed to enhance the anti-cancer effects of other cancer treatments like chemotherapy by reversing tumors – a process where cancer cells lose their malignance – and bring down chronic inflammation. It is a plasmid – circular DNA – that encodes the gene p62.
“The p62 protein is present in all cells. Cancer cells, however, cannot survive without it. Moreover, cancer cells overexpress p62, which protects them from chemo- and radiation therapy. We can induce an immune response when we inject a DNA or RNA drug with a gene encoding p62 into a muscle. Then, a vaccine-induced immune response would find and eliminate in the body the cells that express elevated levels of p62 – the cancer cells,” said Alexander Shneider, founder of CureLab Oncology, in a report published by eCancer.
If the cancer cells were to stop producing p62 due to a mutation, they would be “very susceptible to therapies,” Shneider added.
According to a study published in Frontiers in Oncology, researchers at Curelab showed that disease progression was delayed in patients with stage 3 and 4 platinum-resistant ovarian cancer who received Elenagen in combination with a chemotherapy drug, compared to chemotherapy alone.
Can Ultimovacs’ UV1 bounce back?
Also in the making is Norwegian biotech Ultimovacs’ ovarian cancer vaccine. Unlike OvarianVax, which is currently focused on people who are BRCA-positive, Ultimovacs has set out to treat those who are BRCA-negative. Its cancer vaccine UV1 is designed to prompt a T-cell response against the enzyme telomerase, which is active in most cancer cells. UV1 is being tested along with a checkpoint inhibitor and a PARP inhibitor, across 35 hospitals in 10 European countries. The phase 2 readout is expected early next year.
Ultimovacs is banking on the hopeful success of this trial as things haven’t been going too well for the biotech of late. It tanked a head and neck cancer study of UV1, and has cut short its cash runway, which lasts until early 2026.
As the development of cancer vaccines to combat ovarian cancer continues, the U.S. Food and Drug Administration’s (FDA’s) director of the Center for Biologics Evaluation and Research (CBER) Peter Marks recently expressed that the U.S. regulator is “open for business” when it comes to reviewing cancer vaccines, at the 2024 World Vaccine Congress. Although an ovarian cancer vaccine is yet to be approved, this is encouraging for developers advancing their clinical candidates in the U.S., like the American medical center Mayo Clinic.
Cell therapy vaccine turns patients cancer-free
Its cell therapy vaccine is being studied in a “one-two punch” approach to hamper disease progression in ovarian cancer. Blood is drawn from people whose ovarian cancer has relapsed after standard surgery and chemotherapy. White blood cells are taken from the blood and engineered to become dendritic cells, which are a special kind of immune cell that can trigger the immune system to recognize and fight cancer. These dendritic cells are then returned back to the patient, making it a personalized vaccine.
Building on research from a phase 1 trial where the vaccine improved patient survival rate and 40% of the patients have been cancer-free for nearly 10 years, the vaccine drives Th17 immunity. Th17 cells in ovarian cancer help tackle immune suppression.
“To our knowledge, nobody else has ever deliberately tried to make a Th17 immune response using a cancer vaccine. It targets a new part of the immune system that fights infection and activates a defense mechanism,” said Keith Knutson, co-principal investigator of the study, in a press release last year. “We want to learn if that immune response is more helpful to ovarian cancer patients who have relapsed than other types of immune responses.”
Phase 2 trials are ongoing in Minnesota and will decide whether the vaccine has a chance of approval.
Although a vaccine for ovarian cancer is nowhere near being approved, it is encouraging to see different approaches trialed in the clinic, in hopes that patients get the long-awaited care that they need.
New therapies related to ovarian cancer
- Vaccine Therapy for Treatment of Endometrial and Ovarian Cancer – Henry Jackson Foundation
- Ovarian Cancer Antibody Therapeutic – Cleveland Clinic
- Tumor Mitochondria Vaccine for the Treatment of Cancer – University of Pennsylvania
