Possibilities for personalized vaccines revealed at ESMO symposium

November 21, 2014

Lugano/Geneva, Switzerland, 21 November 2014 - The possibilities for personalised vaccines in all types of cancer are revealed today in a lecture from Dr Harpreet Singh at the ESMO 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 recognised by T-cells," said Singh, who is scientific coordinator of the EU-funded GAPVAC phase I trial which is testing personalised 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 personalised antigens."1

For all patients in the GAPVAC study, researchers will identify genes expressed in the tumour, 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 personalised 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 they express and which their immune system can mount a response to.

Singh said: "A patient may express 20 of these 72 targets on their tumour, 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."

The second vaccine is synthesised de novo based on a mutated peptide expressed in the tumour 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 personalised fashion in a way that I think has never been done for any patient."

He added: "GAPVAC has two major goals. One is to show that personalised 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-personalised antigens."

Singh's previous research has shown that vaccination with non-personalised antigens leads to better disease control and longer overall survival in phase I and phase II clinical studies in patients with renal cell cancer.2

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

He added: "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 personalised 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 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 personalised aspect is just based on the low abundance of Her2, the target."

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

He concluded: "Personalisation 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 personalised antigens in adoptive cell therapy."
Notes and references

1 Glioma Actively Personalised Vaccine Consortium (GAPVAC): http://www.gapvac.eu

2 Walter S, et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med. 2012;18(8):1254-1261. doi: 10.1038/nm.2883. Epub 2012 Jul 29.


"Novel cancer antigens for personalised immunotherapies" - Friday, November 21 - Session 3 - 13:10 CET.


Information contained in this press release was provided by the abstracts authors and reflects the content of the studies. It does not necessarily express ESMO's point of view.

About the European Society for Medical Oncology

The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care.

ESMO's mission is to advance cancer care and cure through fostering and disseminating good science that leads to better medicine and determines best practice.

ESMO's scientific journal, Annals of Oncology, ranks among the top clinical oncology journals worldwide. ESMO events are the meeting place in Europe for medical oncologists to update their knowledge, to network and to exchange ideas.

To find out more about ESMO, please visit: http://www.esmo.org

European Society for Medical Oncology

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.