Abstract 88MO
Background
Triple negative breast cancer (TNBC) presents with an aggressive clinical phenotype lacking expression of conventional drug targets. Overall survival in early- and advanced-stage disease is poor.
Methods
TNBC-MERIT is a phase I trial (NCT02316457) assessing the feasibility, safety and immunogenicity of a liposome-formulated intravenous RNA vaccine encoding different tumor antigen categories in TNBC patients after surgery and (neo-)adjuvant chemotherapy. Patients in two arms of this trial received a personalized set of pre-manufactured non-mutated shared tumor-associated antigens with or without universal T helper epitopes. In a third arm, patients were vaccinated with IVAC_M_uID, an on-demand manufactured Individualized NeoAntigen Specific Immunotherapy (iNeST) encoding neoepitopes derived from up to 20 cancer mutations determined by NGS. This report provides a preliminary data analysis of immune responses in IVAC_M_uID-vaccinated patients as analyzed by IFNγ-ELISpot, multimer staining, TCR repertoire profiling and single cell TCR sequencing (data final mid-2020).
Results
Immunogenicity data was generated from all 14 IVAC_M_uID-treated patients. All analyzed patients had vaccine-induced CD4+ and/or CD8+ T-cell responses against 1 to 10 of the vaccine neoepitopes detected by IFNγ ELISpot, ex vivo or after in vitro stimulation. A substantial number of T-cell responses against individual neoepitopes were induced de novo and of high magnitude (up to 10.3% of peripheral CD8 T cells). One of the index patients characterized in more detail mounted CD4+ and/or CD8+ T-cell responses against 10 of 20 vaccine neoepitopes. The highly poly-epitopic TCR-clonotype diversified CD8+ T-cell response comprised in aggregate about 30% of total peripheral CD8+ T cells and was sustained at high levels for at least 6 months after the last vaccination. Vaccine-induced CD8+ T cells were of effector/memory, PD1+ phenotype, with a high fraction IFNγ/TNFα/Mip-1a&b triple-positive.
Conclusions
This preliminary data suggests that the iNeST IVAC_M_uID is highly efficient in inducing strong poly-epitopic T-cell responses in patients with TNBC in the post-(neo) adjuvant setting.
Clinical trial identification
NCT02316457.
Editorial acknowledgement
Legal entity responsible for the study
BioNTech SE.
Funding
BioNTech SE.
Disclosure
M. Schmidt: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Research grant/Funding (self): BioNTech SE; Research grant/Funding (self): Genentech. I. Vogler: Full/Part-time employment: BioNTech RNA Pharmaceuticals GmbH. E. Derhovanessian: Full/Part-time employment: BioNTech SE. T. Omokoko: Full/Part-time employment: BioNTech Cell & Gene Therapies GmbH. E. Godehardt: Full/Part-time employment: BioNTech RNA Pharmaceuticals GmbH. A. Cortini: Full/Part-time employment: BioNTech Cell & Gene Therapies GmbH. S. Newrzela: Full/Part-time employment: BioNTech Cell & Gene Therapies GmbH. J. Grützner: Full/Part-time employment: BioNTech SE. S. Bolte: Full/Part-time employment: BioNTech SE. D. Langer: Full/Part-time employment: BioNTech SE. T. Sjöblom: Shareholder/Stockholder/Stock options, Officer/Board of Directors: Exscale Biospecimen Solution A. Ö. Türeci: Leadership role, Officer/Board of Directors: BioNTech SE. U. Sahin: Leadership role, Officer/Board of Directors: BioNTech SE. All other authors have declared no conflicts of interest.
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