Oxford's cancer vaccine/immunotherapy combo to head for human trials
Scientists at Oxford have demonstrated a powerful pairing – a cancer vaccine and immunotherapy. In tests in mice, the vaccine boosted levels of tumor-hunting immune cells, while the immunotherapy made them more effective killers. Human trials are due to start later this year.
The human immune system is a powerful front-line of defense, patroling our bodies for foreign invaders like viruses and bacteria, as well as rogue cells stepping out of line that could become cancerous. Unfortunately, cancer has a variety of underhanded techniques to escape detection by the immune system.
Immunotherapy aims to give our bodies the upper hand once again, supercharging immune cells to better fight cancers. One way to do this is to remove the natural “checkpoints” that stop immune cells from going too wild, and while this technique has shown promise fighting some forms of cancer, results have been less encouraging for others.
The problem, it seems, is that letting a patient’s immune cells off the leash is still limited by how many of those immune cells there are in the first place. So boosting those numbers is what the cancer vaccine is designed to do.
The Oxford team developed a two-dose therapeutic cancer vaccine, using one of the same viral vectors used in the Oxford-AstraZeneca vaccine for COVID-19. The vaccine increases the levels of CD8+ T cells, which are primed to target two proteins called MAGE-A3 and NY-ESO-1, which only appear on the surface of cancer cells.
“MAGE proteins have an advantage over other cancer antigens as vaccine targets since they are present on a wide range of tumor types,” says Benoit Van den Eynde, an author of the study. “This broadens the potential benefit of this approach to people with many different types of cancer. Importantly for target specificity, MAGE-type antigens are not present on the surface of normal tissues, which reduces the risk of side effects caused by the immune system attacking healthy cells.”
The researchers paired this vaccine with immunotherapy, and tested the combination in mice. As hoped, the vaccine increased levels of CD8+ T cells, while the immunotherapy allowed them to target tumors more aggressively. Together, the two techniques greatly reduced the tumor size and improved the survival rate of the mice, compared to control mice or the immunotherapy alone. Half of the mice in the test group were still alive at the 50-day mark, while none of the control group survived 30 days.
The team says that this combination could be used in humans – and in fact, a Phase 1/2a clinical trial is set to begin later this year, in 80 patients with non-small cell lung cancer.
“Our cancer vaccines elicit strong CD8+ T cell responses that infiltrate tumors and show great potential in enhancing the efficacy of immune checkpoint blockade therapy and improving outcomes for patients with cancer,” says Adrian Hill, co-author of the study.
This new work adds further evidence to a growing body of research showing how powerful a combo cancer vaccines and immunotherapy can be. An MIT study a few years ago used a vaccine booster to improve a different type of immunotherapy called CAR T cell therapy. Another used a drug to reactivate immune cells that cancer had disabled, and backed it up with checkpoint blockers. And just a few months ago, the University of Konstanz reported that checkpoint blockers aided the effects of a vaccine made up of tumor proteins and a molecule called riboxxim.
The new study was published in the Journal for Immunotherapy of Cancer.
Source: Oxford University
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