GENEVA, SWITZERLAND-Anticancer vaccines have gained a new lease of life with techniques to personalize them to individual patients. Cutting-edge developments in this re-energized field were revealed at the 2018 ESMO Immuno-Oncology Congress.
The original anticancer vaccines, launched in the late 1990s, were based on shared tumor antigens and failed to induce a potent immune response. After decades of disappointing results, a number of advances have sparked a renewed interest in the field. These include new technologies and prediction algorithms to personalize vaccines, and the introduction of checkpoint inhibitors for combination therapy
"The 'modern anticancer vaccines' session at the ESMO Immuno-Oncology Congress was timely since there is again a flurry of activity around anticancer vaccines," noted Michal Bassani-Sternberg, PhD, Group Leader, Immunopeptidomics, Hi-TIDe Laboratory, Department of Oncology, University of Lausanne, Switzerland, and the Ludwig Institute for Cancer Research in Lausanne. "We can now customize vaccines for each patient based on the genomic information in their tumor, and the early results are promising."
Personalization has been made possible with high-throughput next-generation sequencing. This technology identifies mutations that are unique to a patient's tumor and are not found elsewhere in the body, meaning that a vaccine mounts a local immune response. Algorithms can predict which neoantigens should be targeted for vaccination.
"We have a good way to fish out and propose targets for vaccination," Bassani-Sternberg stated. "The first trials were published last year and showed that the selected targets were immunogenic, meaning that vaccination induced immune responses or amplified existing immune responses against these neoantigens. In addition, the vaccines worked well with checkpoint inhibitors. We now need to see if vaccination against neoantigens leads to tumor regression."
Neoantigens were explored in a dedicated session at the ESMO Immuno-Oncology Congress and were discussed in the session on modern anticancer vaccines, which also described the role of other vaccine targets. These include oncogenic proteins such as HER2, pathogens like HPV, and prostate-specific antigens. These shared antigens are also being tested in combination with checkpoint inhibitors.
Bassani-Sternberg said the combination of modern anticancer vaccines and checkpoint inhibitors appears to generate the most effective immune response. "Vaccines can induce new responses in patients with 'cold tumors' which lack immune cells, thus making the environment receptive to check point inhibitors," she said.
Numerous questions remain unanswered, such as when to vaccinate patients. Should this be immediately after surgery, when there are few tumor cells left, or beforehand? Should vaccines be administered against primary tumors and metastases? Will it be necessary to give new vaccines every few months as tumors evolve naturally and in response to treatment? How and when should vaccines be combined with other therapies?
But despite these questions, vaccination appears feasible. The technology to develop vaccines is available and getting better, the vaccines are safe and immunogenic, and there is openness from the regulators to testing vaccines in clinical trials.
"We are counting on new technologies that have now matured," Bassani-Sternberg noted. "Next-generation sequencing has made identification of vaccine targets more efficient, reliable, and cheaper. The algorithms to interpret this data are benchmarked and validated for predicting which targets are most likely to be immunogenic. Sequencing technologies are only going to get better and prediction tools will become even more accurate."
"There is great hope for vaccines," she continued. "And they have the potential to benefit most patients because almost all tumors have targets that could be vaccinated."