36P - UV1 - A peptide-based, therapeutic cancer vaccine targeting the reverse transcriptase subunit of human telomerase (hTERT)

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Else Marit Inderberg
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors E.M. Inderberg1, W. Lilleby2, T.K. Guren3, P.F. Brunsvig3, K. Lislerud1, A. Tornes4, G. Gaudernack4
  • 1Dept. Of Cellular Therapy, Oslo University Hospital- The Norwegian Radium Hospital, 0379 - Oslo/NO
  • 2Dept. Of Oncology And Radiotherapy, Oslo University Hospital- The Norwegian Radium Hospital, 0379 - oslo/NO
  • 3Department Of Oncology, Oslo University Hospital, 0424 - Oslo/NO
  • 4Research And Development, Ultimovacs AS, Oslo/NO

Abstract

Aim/Background

Patients with objective clinical response after treatment with a peptide-based, therapeutic cancer vaccine provide a unique opportunity to identify the immunological characteristics underlying tumour regression. We screened a library of long, overlapping hTERT peptides using blood samples from long-term surviving cancer patients vaccinated with different types of first-generation hTERT vaccines. Strong immune responses were observed against multiple hTERT epitopes not present in the vaccines given, thus demonstrating epitope spreading. Based on this, three long, wild-type hTERT fragments representing the novel epitopes most frequently recognized were selected as components of the UV1 vaccine. The composition of epitopes embedded in the three UV1 peptides indicates a high population coverage, and the long UV1 peptides are shown to stimulate both CD8+ cytotoxic T cells and CD4+ T helper cells. Consequently, we hypothesized that vaccination with UV1 may give a broader and stronger immune response in more patients than the first generation hTERT vaccine, and therefore provide clinical benefit in a larger proportion of patients.

Methods

UV1 is currently being investigated in three phase I/IIa trials (n = 52) in patients with metastatic prostate cancer [EudraCT No. 2012-002411-26], non-small cell lung cancer (NSCLC) [EudraCT No. 2012-00185220] and metastatic melanoma [EudraCT No. 2013-005582-39] in combination with ipilimumab. UV1 is given as intradermal injections with GM-CSF as adjuvant.

Results

Analyses of immune responses across studies showed a faster response and higher immunological response rate (86%) in newly diagnosed prostate cancer patient compared to heavily treated NSCLC patients (67%). Preliminary data indicate the highest response rate in melanoma (90%), suggesting a synergistic effect of UV1 vaccination combined with ipilimumab.

Conclusions

The broad population coverage by the UV1 vaccine most likely reflects that the selected peptides are highly immunogenic across different HLA haplotypes, thus making it a “universal” cancer vaccine. Clinical data substantiating a link between vaccine specific immunological response and clinical benefit is awaited.

Clinical trial identification

Metastatic prostate cancer [EudraCT No. 2012-002411-26], non-small cell lung cancer (NSCLC) [EudraCT No. 2012-00185220] and metastatic melanoma [EudraCT No. 2013-005582-39] in combination with ipilimumab.

Legal entity responsible for the study

Ultimovacs AS

Funding

Ultimovacs AS

Disclosure

E.M. Inderberg: Inventor on the UV1 vaccine patent. A. Tornes: Employee and sharholder of Ultimovacs AS. G. Gaudernack: Inventor on UV1 patent, employee and shareholder of Ultimovacs AS. All other authors have declared no conflicts of interest.