A presentation given by Harpreet Singh (Immatics Biotechnologies GmbH; Tuebingen, Germany) at the European Society for Medical Oncology Symposium on Immuno-Oncology 2014 (21–22 November, Geneva, Switzerland) has shed light on the possibilities of personalized vaccines for cancer treatment. Finding appropriate cancer targets that can be recognized by T cells has proven to be one of the biggest difficulties in cancer immunotherapy research to date.
Harpreet Singh is coordinating the ongoing EU-funded Phase I GAPVAC trial, which is currently testing the use of personalized vaccines in glioblastoma, the most aggressive form of brain cancer.
Singh commented: “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 non-personalized antigens.”
In the trial, Singh and his team will treat glioblastoma patients with vaccines that are ‘personalized’ for each patient. They will gather data from the patients prior to therapy, including information concerning: genes expressed in the tumor, peptides presented on the human leukocyte antigen receptor (which will be seen by T cells), and cancer specific mutations. In addition to this, the researchers will examine the ability of the immune system to respond to certain antigens.
Subsequent to gaining this information, two vaccines containing personalized antigens termed actively personalized vaccines (APVACs) will then be constructed and administered to patients following conventional surgery.
The first vaccine will be prepared from an established warehouse of 72 targets previously identified by the researchers as potentially relevant for treatment in glioblastoma. Patients will be given a cocktail of the peptides expressed by their tumors, which their immune system can mount a response to.
The second vaccine will be synthesized de novo based on a mutated peptide expressed in the tumor of the individual patient. Singh commented: “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.”
In previous research carried out by Singh and his team, off-the-shelf peptide targets, which were shared by many patients with a certain cancer, were used. Their work demonstrated that vaccination with non-personalized antigens lead to increased disease control and longer overall survival in Phase I and Phase II clinical studies in patients with renal cell cancer.
During this research they identified other targets that appeared in very few or even, in extreme circumstances, in a single patient. This led the team to start developing personalized cancer vaccines that contain the ideal set of targets for one particular patient. As rarer peptides are often of higher quality, the team hope that their use will result in more effective vaccines than those previously ‘off-the-shelf’.
Singh continued: “A very simple example from something established is trastuzumab in breast cancer. Trastuzumab was originally given to every breast cancer patient and the efficacy was just seen in a subset. Now only about 20% of breast cancer patients receive trastuzumab and the personalized aspect is just based on the low abundance of HER2, the target.”
The team believe that personalized vaccines hold possibilities for all types of cancer and that personalization could also be extended to other therapies.
Singh concluded: “Personalization is not limited to vaccines but is a general principle that could be applied to cancer immunotherapy more broadly. We are starting with vaccines but we are also thinking about how to use personalized antigens in adoptive cell therapy.”