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With New Study, Personalized Cancer Vaccines Edge Closer to Reality

GAPVAC trial matches vaccines to individual glioblastoma patients

A study that is testing personalized vaccines for glioblastoma may help chart a course for such tailored treatments in all types of cancer, researchers learned at the European Society for Medical Oncology Symposium on Immuno-Oncology 2014 in Geneva, Switzerland.

 For all patients in the GAPVAC phase I trial, researchers will identify genes expressed in the tumor, peptides presented on the human leukocyte antigen (HLA) receptor (i.e., peptides which 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 be vaccinated in patients. Patients will be given a cocktail of the peptides that they express and that their immune system can mount a response to.

“One of the biggest hurdles in cancer immunotherapy is the discovery of appropriate cancer targets that can be recognized by T cells,” Dr. Harpreet Singh, scientific coordinator of the European Union-funded GAPVAC trial, said in a lecture at the ESMO symposium. “In the GAPVAC trial we will treat glioblastoma patients with vaccines that are ideal for each patient because they contain personalized antigens.”

A patient might express 20 of the 72 known targets on their tumor, for example. “If we find that the patient's immune system can mount responses to five of the 20 targets, we mix the five 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.”

The second vaccine is synthesized de novo based on a mutated peptide expressed in the tumor of the patient, Singh said: “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,” he added. “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 non-personalized antigens.”

Singh's previous research has shown that vaccination with nonpersonalized antigens leads to better disease control and longer overall survival in phase I and phase II clinical studies in patients with renal cell cancer.

“For the nonpersonalized vaccines, we used off-the-shelf peptide targets that were shared by many patients with a particular cancer,” said Singh. “Using this approach we have successfully vaccinated patients with renal cell cancer, colorectal cancer, and glioblastoma.”

“During this research we identified other targets that appeared in very few patients or even, in extreme cases, in a single patient. Often these rarer peptides are of better quality, meaning they are more specifically seen in cancer cells and occur at higher levels. This led us to start developing personalized cancer vaccines, which contain the ideal set of targets for one particular patient. We hope they will be even more effective than the off-the-shelf vaccines.”

Singh believes that personalized vaccines hold promise for all types of cancer, and that personalization could also be applied to adoptive cell therapy.

“Personalization is not limited to vaccines but is a general principle that could be applied to cancer immunotherapy more broadly,” he said. “We are starting with vaccines but we are also thinking about how to use personalized antigens in adoptive cell therapy.”

Source: ESMO; November 21, 2014.

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