PO-486 Surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimised EGF-based vaccination schedule
IntroductionIn previous clinical trials were reported that an EGF-based vaccine administration was immunogenic in advanced non-small cell lung cancer (NSCLC) patients and the elicited immune response was associated with patient´s survival. However, the description of additional key features associat...
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| Published in: | ESMO open Vol. 3; no. Suppl 2; p. A420 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Elsevier Ltd
01-07-2018
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| Online Access: | Get full text |
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| Summary: | IntroductionIn previous clinical trials were reported that an EGF-based vaccine administration was immunogenic in advanced non-small cell lung cancer (NSCLC) patients and the elicited immune response was associated with patient´s survival. However, the description of additional key features associated with a ‘protective’ humoral response, using an optimised immunisation schedule, remained unknown.Material and methodsA phase III trial was designed using an optimised immunisation schedule. It included higher antigen dose and injections at multiple vaccination sites. Immune response and circulating biomarkers were studied in a subset of patients. EGF-specific antibody titers, IgG subclasses and peptide immunodominance was assessed by ELISA. In vitro EGF-neutralisation capacity of immune sera was evaluated by Western Blot and EGF-IgG binding kinetics by surface plasmon resonance (SPR) technology. Additionally, circulating levels of EGFR ligands (EGF, TGFα, AR) and others NSCLC- associated circulating factors were measured.Results and discussionsEGF vaccine administration elicited antibody titers higher than 1:4000 in 80% of vaccinated patients after 3 months of treatment. The EGF-specific humoral response was directed against the central region of the EGF molecule and was mainly composed by IgG3/IgG4 antibody subclasses. The capacity of post-immune sera to inhibit EGFR phosphorylation increased during the course of the immunisation scheme and was associated with EGF-specific antibody affinity maturation. Basal concentrations of EGF and TGFα in the serum were affected by EGF- based immunisation. The avidity and the EGFR phosphorylation inhibition capacity of elicited polyclonal antibodies was associated with the clinical benefit of treated patients.ConclusionOptimising the vaccination schedule allowed to induce the development of a protective humoral response in a high percent of NSCLC vaccinated patients. Quality of induced anti-EGF polyclonal antibodies was associated with clinical benefit (clinical trial registration number: RPCEC00000161). |
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| ISSN: | 2059-7029 2059-7029 |
| DOI: | 10.1136/esmoopen-2018-EACR25.988 |