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T cell Bispecific Antibodies in Node-Positive Breast Cancer: Novel Therapeutic Avenue for MHC class I Loss Variants

Messaoudene, M; Mourikis, TP; Michels, J; Fu, Y; Bonvalet, M; Lacroix-Trikki, M; Routy, B; ... Zitvogel, L; + view all (2019) T cell Bispecific Antibodies in Node-Positive Breast Cancer: Novel Therapeutic Avenue for MHC class I Loss Variants. Annals of Oncology 10.1093/annonc/mdz112. (In press).

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Abstract

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) represent a prognostic factor for survival in primary breast cancers (BC). Nonetheless, neoepitope load and TILs cytolytic activity are modest in BC, compromising the efficacy of immune-activating antibodies, which do not yet compete against immunogenic chemotherapy. PATIENTS AND METHODS: We analyzed by functional flow cytometry the immune dynamics of primary and metastatic axillary nodes (mLN) in early breast cancers after exposure to T cell bispecific antibodies (TCB) bridging CD3ε and HER2 or CEACAM5, before and after chemotherapy. HLA class I loss was assessed by whole exome sequencing and immunohistochemistry. 100 primary BC, 64 surrounding "healthy tissue" (HT) and 24 mLN related-parameters were analyzed. RESULTS: HLA loss of heterozygosity was observed in early BC, at a clonal and subclonal level and was associated with regulatory T cells and Tim3 expression restraining the immuno-stimulatory effects of neoadjuvant chemotherapy. TCB bridging CD3ε and HER2 or CEACAM5 could bypass MHC class I loss, partially rescuing T cell functions in mLN. CONCLUSION: TCB should be developed in BC to circumvent low MHC/peptide complexes.

Type: Article
Title: T cell Bispecific Antibodies in Node-Positive Breast Cancer: Novel Therapeutic Avenue for MHC class I Loss Variants
Location: England
DOI: 10.1093/annonc/mdz112
Publisher version: https://doi.org/10.1093/annonc/mdz112
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Breast cancer, CEACAM5, HER2, HLA loss, T cell bispecific antibodies (TCB), Tumor-infiltrating lymphocytes (TILs)
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/10072350
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