The possibilities for personalized vaccines in all types of cancer were revealed in a lecture at the European Society for Medical Oncology Symposium on Immuno-Oncology 2014 in Geneva, Switzerland.
“One of the biggest hurdles in cancer immunotherapy is the discovery of appropriate cancer targets that can be recognized by T-cells,” said Harpreet Singh, PhD, scientific coordinator of the European Union-funded GAPVAC phase I trial that is testing personalized vaccines in glioblastoma, the most common and aggressive brain cancer. “In the GAPVAC trial we will treat glioblastoma patients with vaccines that are ideal for each patient because they contain personalized antigens.”
For all patients in the GAPVAC study, researchers will identify genes expressed in the tumor, peptides presented on the human leukocyte antigen (HLA) receptor (ie, peptides that will be seen by T-cells), cancer specific mutations, and the ability of the immune system to mount a response to certain antigens. Based on this information, two vaccines, called actively personalized vaccines (APVACs), will be constructed and administered following conventional surgery.
The first vaccine will be prepared from a warehouse of 72 targets previously identified by the researchers as relevant for treatment in glioblastoma. These peptides have been manufactured and put on the shelf ready to vaccinate patients. Patients will be given a cocktail of the peptides they express and that their immune system can mount a response to.
“A patient may express 20 of these 72 targets on their tumor, for example. If we find that the patient’s immune system can mount responses to 5 of the 20 targets, we mix the 5 peptides and give them to the patient. We mix the peptides off the shelf but the cocktail is changed for each patient because it is matched to their biomarkers,” said Singh.
The second vaccine is synthesized de novo based on a mutated peptide expressed in the tumor of the patient. Singh explained, “That peptide is not in our warehouse because it just occurs in this one single patient. The patient receives APVAC-1 and APVAC-2 in a highly personalized fashion in a way that I think has never been done for any patient.”
“GAPVAC has two major goals. One is to show that personalized vaccines are feasible, since this is one of the most complicated trials ever done in cancer immunotherapy. The second is to show that we can mount far better biological responses in these patients compared to vaccination with nonpersonalized antigens.”