Abstract 3297
Background
Most therapeutic vaccine clinical trials (CTs) have failed to prove efficacy, even if immunogenicity was confirmed earlier. It was already shown that immune responses generated against multiple antigens are indicative of clinical responses. We aimed to find association between the heterogeneity of immune response and clinical efficacy and, based on this develop a tool that can predict the clinical outcome of cancer vaccines.
Methods
In an extensive literature search we collected the immune- and objective response rates (IRR, ORR) of 94 CTs in which 2,338 patients were treated with 64 different vaccines. Vaccine sequences were used to predict personal epitopes (PEPIs) that bind to at least 3 HLA alleles of the same subject, for all patients of a representative model population. Then we determined the percentage of subjects with at least 1 vaccine specific PEPIs (PEPI Score) and at least 2 vaccine specific PEPIs derived from different antigens (MultiAg PEPI-Score) and compared to the published IRR and ORR.
Results
PEPI Score was able to predict the immunogenicity of therapeutic vaccines; significant correlation was found with IRR (p = 0.002). As expected, no correlation was found between ORR and IRR (p = 0.294), neither between PEPI Score and ORR (p = 0.302), suggesting, that immune response against a single epitope is not enough for efficient tumor response. However, we found that MultiAg PEPI-Score significantly correlates with ORR (p < 0.0001) consistent with earlier findings that the targeting of multiple antigens is required for tumor shrinkage.
Conclusions
Our results demonstrate that both IRR and ORR can be predicted by PEPIs. For clinical efficacy it is crucial to target and generate immune response against multiple antigens. Based on our analysis our computational model is useful and accurate for the prediction of the clinical outcome of cancer vaccines and can even be suitable for rescuing CTs with insufficient or missing responder selection.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
O. Lorincz: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. J. Toth: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. M. Megyesi: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. K. Pántya: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. E. Somogyi: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. Z. Csiszovszki: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. P. Pales: Full / Part-time employment: Treos Bio Zrt. L. Molnar: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. E.R. Tőke: Shareholder / Stockholder / Stock options, Officer / Board of Directors: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. All other authors have declared no conflicts of interest.
Resources from the same session
2963 - Analytical performance of the Resolution-HRD plasma assay used to identify mCRPC patients with biallelic disruption of DNA repair genes for treatment with niraparib
Presenter: Ira Pekker
Session: Poster Display session 3
Resources:
Abstract
3523 - Results of a global external quality assessment scheme for EGFR testing on liquid biopsy
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3295 - Clinical impact of plasma Next-Generation Sequencing (NGS) in advanced Non-small cell lung cancer (aNSCLC)
Presenter: Laura Bonanno
Session: Poster Display session 3
Resources:
Abstract
5632 - Feasibility study of a ctEGFR prototype assay on the fully automated Idylla™ platform
Presenter: Martin Reijans
Session: Poster Display session 3
Resources:
Abstract
3614 - Enhanced Access to EGFR Molecular Testing in NSCLC using a Cell-Free DNA Tube for Liquid Biopsy
Presenter: Theresa May
Session: Poster Display session 3
Resources:
Abstract
5664 - Analysis of circulating tumor DNA in paired plasma and sputum samples of EGFR-mutated NSCLC patients
Presenter: Christina Grech
Session: Poster Display session 3
Resources:
Abstract
4945 - Liquid biopsy and Array Comparative Genomic Hybridization (aCGH)
Presenter: Panagiotis Apostolou
Session: Poster Display session 3
Resources:
Abstract
5746 - Next-generation sequencing panel verification to detect low frequency single nucleotide and copy number variants from mixing cell line studies
Presenter: Rocio Rosas-Alonso
Session: Poster Display session 3
Resources:
Abstract
5901 - Automated rarefaction analysis for precision B and T cell receptor repertoire profiling from peripheral blood and FFPE-preserved tumor
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
2027 - A Heptamethine cyanine dye is a potential diagnostic marker for Myeloid-Derived Suppressor Cells
Presenter: Chaeyong Jung
Session: Poster Display session 3
Resources:
Abstract