65P - T cell recognition of breast cancer antigens (65P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Complications of Treatment
Cancer Immunology and Immunotherapy
Palliative and Supportive Care
Presenter Sofie Ramskov
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors S. Ramskov1, N. Viborg Petersen1, R. Sick Andersen2, P. Thor Straten3, I. Svane3, Ö. Met3, S. Reker Hadrup4
  • 1Division Of Immunology & Vaccinology - T-cells & Cancer, Technical University of Denmark, 2800 - Kongens Lyngby/DK
  • 2Department Of Cancer And Inflammation Research, South Danish University, Odense C/DK
  • 3Center For Cancer Immune Therapy, Herlev and Gentofte Hospital, Herlev/DK
  • 4Division Of Immunology & Vaccinology - T-cells & Cancer, Technical University of Denmark, Kongens Lyngby/DK

Abstract

Background

Despite originally considered an immunologically silent malignancy, recent studies are encouraging research of breast cancer immunogenicity to evaluate the applicability of immunotherapy as a treatment strategy. The epitope landscape in breast cancer is minimally described. Consequently, this project investigates four proteins commonly upregulated in breast cancer and thus probable tumor associated antigens (TAAs). Aromatase, prolactin, never in mitosis a related kinase 3 (NEK3), and protein inhibitor of activated STAT3 (PIAS3) contribute to increased growth, survival, and motility of malignant cells.

Methods

Aspiring to uncover novel epitopes for cytotoxic T cells, a reverse immunology approach was applied. In silico screening via NetMHC was used to predict binding of peptides within the proteins to HLA-A*0201 and -B*0702. Next, an MHC ELISA was applied to experimentally confirm which of the peptides are indeed HLA-A*0201 and -B*0702 binders. Hereafter, a novel method for high throughout detection of antigen specific T cells was applied. Via DNA barcode labeled MHC multimer technology, parallel screening for T cell recognition of all predicted MHC binding peptides was performed.

Results

415 peptides were predicted in silico as HLA-A*0201 and -B*0702 binders. Subsequent in vitro binding analysis confirmed binding for 147 of the 415 predicted binders. The 147 peptides were evaluated for T cell recognition utilizing DNA barcode labeled MHC multimers to screen peripheral blood lymphocytes from breast cancer patients and healthy donor samples. Significantly more TAA specific T cell responses were detected in breast cancer patients compared to healthy donors for both HLA-A*0201 (p 

Conclusions

Thus, the inspected proteins; aromatase, prolactin, NEK3 and PIAS3, indeed contain targets for T cell reactivity.

Clinical trial identification

Legal entity responsible for the study

Sine Reker Hadrup

Funding

Danish Cancer Society, Danish Council for Independent Research

Disclosure

All authors have declared no conflicts of interest.