NEUVOGEN’s official strategy revolves around covering the entire immune system so that the tumor cannot perform an “immune escape”. Past immune priming efforts have fallen short because they focus on only a handful of important targets that some tumor cells may not express, thereby allowing them to escape the therapy’s boundaries.
Cancer is the second leading cause of death worldwide, so the theory of preventing it before it occurs makes a lot of sense. The global cancer vaccines market stood at $5.68 billion in 2019 and was projected to grow to $24.32 billion by 2030. Here are just a few of the companies trying to make that happen, and a look at their recent strides toward a vaccine.
No Escape for Tumors With NEUVOGEN
San Diego-based NEUVOGEN Inc, which is developing therapeutic whole cell vaccines for solid tumors, today announced its Next Generation Cancer Vaccine Strategy to revolutionize how solid tumors are treated.
NEUVOGEN’s official strategy revolves around covering the entire immune system so that the tumor cannot perform an “immune escape”. Past immune priming efforts have fallen short because they focus on only a handful of important targets that some tumor cells may not express, thereby allowing them to escape the therapy’s boundaries.
NEUVOGEN is also augmenting each of its vaccines with a proprietary combination of genetic modifications to create a robust immune priming adjuvant effect and overcome peripheral tolerance to self-antigens.
“The NEUVOGEN whole cell platform has the ability to transform the clinical landscape of how we treat patients with solid tumors. Our scientists have been able to employ multiple direct killing mechanisms of cancer therapeutics and we are confident that NEUVOGEN’s systems approach will maximize immune priming while minimizing immune escape of solid tumors. NEUVOGEN will generate potentially safer and more effective therapies with the goal of targeting all of the cells within the tumor, thereby driving sustained remissions and eliminating cancer recurrences,” said NEUVOGEN Chief Medical Officer, Mark Bagarazzi.
The company has backers with a lot of gravitas, such as Gordon Binder, the former chief executive officer of biotech giant, Amgen, and Chairman of the Board at NEUVOGEN.
“NEUVOGEN has emerged as a leader to watch in the immuno-oncology space. Given my experience in oncology treatments, NEUVOGEN’s management team has made impressive progress,” said Binder.
Lineage Leveraging Dendritic Cells in Cancer Vaccine Platform
California-based Lineage Cell Therapeutics is developing an allogeneic, non-patient specific cancer vaccine candidate called VAC2, designed to educate and amplify a patient’s own immune response to foreign material such as tumor cells.
“Dendritic cells of course are nature’s most powerful antigen-presenting cell, and if you want to deliver a message to the immune system about some foreign material, it’s hard to do better than to pre-package that information in 60 million dendritic cells and let them loose in the body,” Lineage Chief Executive Officer, Brian Culley told BioSpace. “There’s something called TERT [Telomerase reverse transcriptase] which is highly expressed in tumor cells and rarely expressed in normal cells, so it ends up being a marker. So we express TERT on the surface of these dendritic cells, and in doing so, that’s the mechanism to be able to deliver that message profoundly and aggressively to the immune system.”
In October, Lineage, along with Cancer Research UK, announced promising preliminary results from an ongoing phase I clinical study of VAC2 in non-small cell lung cancer (NSCLC).
Lineage, like many other companies, has been somewhat stalled by the COVID-19 pandemic but expects to complete enrollment in an eight-person clinical trial by the end of this quarter.
“What I’m looking for in that data is further evidence that the patient’s immune system has responded to our specific stimulus,” said Culley. “We’ve seen patients who have two or even more than three percent of their T cells activated against TERT following our stimulus, and that’s 10-40 times higher than conventional methods.”
On the strength of these results, Lineage plans to evaluate the vaccine candidate in combination with therapies that are biologically complementary to it, including chemotherapy and anti-PD1 immunotherapy.
“I think what we’re learning about dendritic cell vaccines is that they don’t work too well on a stand-alone basis, and they might work a lot better in conjunction with chemotherapy or in conjunction with checkpoint inhibitors,” said Culley.
BioNTech Has an mRNA Vaccine Candidate for Cancer Too
A burgeoning space, few therapeutic cancer vaccines have been successful against treatment-resistant tumors in late-stage clinical trials. So who better to break through than Ugur Sahin, Co-founder and Chief Executive Officer of BioNTech?
On July 30, 2020, while the rest of BioNTech was busy with the COVID-19 vaccine, Sahin and his team reported phase I results from a landmark first-in-human dose-escalation phase I trial of FixVac (BNT111) in advanced melanoma.
FixVac is an intravenously administered liposomal mRNA vaccine targeting four non-mutated tumor-associated antigens common in melanoma.
In an interim analysis, Sahin and his team showed that, when deployed in combination with checkpoint inhibitor PD1, FixVac led to durable objective responses in checkpoint-inhibitor-experienced patients with unresectable melanoma. The cautiously optimistic results were accompanied by the presence of strong CD4+ and CD8+ T cell immunity against the vaccine antigens.
Just two days later, BioNTech announced a strategic collaboration with Regeneron Pharmaceuticals to conduct a randomized Phase II study combining FixVac and Regeneron’s Libtayo, a fully human anti-PD-1 therapy, for the treatment of melanoma that has progressed past prior PD1 blockades.
“We believe our FixVac platform represents a powerful new drug class of mRNA immunotherapies against cancer. We look forward to working together with Regeneron to advance this product candidate into potentially registrational clinical trials,” said Sahin.
In addition to melanoma, BioNTech’s FixVac product line, which is designed to enhance stability and translation, target dendritic cells, and trigger both innate and adaptive immune responses, is also being tested in phase 1 against HPV-positive head and neck cancers and triple-negative breast cancers.
A Personalized Cancer Vaccine
Personalized cancer vaccines, where a person’s own cancer cells are deployed to train their immune system to recognize and kill their cancer, appear to be on the cusp of arriving, and academic institutions like the University of Arizona College of Medicine are trying to expedite that.
In November, the college presented preliminary data from a phase I clinical trial sponsored by Moderna, combining a novel personalized cancer vaccine candidate with Merck’s immunotherapy drug, Pembrolizumab (KEYTRUDA), a humanized antibody used in the treatment of head, neck, and lung cancers along with melanoma.
Dr. Julie E. Bauman, chief of the Division of Hematology and Oncology at the college in Tucson and deputy director of the University of Arizona Cancer Center, presented data on the study’s first ten patients with head and neck cancer at the annual meeting of the Society for the Immunotherapy of Cancer.
Five of these first ten patients experienced a clinical response to the personalized vaccine, with two enjoying a complete response (CR) following the treatment.
The 50% response rate was significantly higher than the 15% of patients who received the Pembrolizumab immunotherapy alone.
“The data are preliminary and the sample size is small, but it is promising. A phase I trial is about safety first and foremost, and we now know this treatment is safe and tolerable. But, we also have a strong signal to point us to further study this in head and neck cancer. That is why we are excited to expand this trial,” said Dr. Bauman at the time of the announcement.
Based on the promising results, the trial is set to expand enrollment to 40 patients.
