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
, 30
(6)
pp. 934-944.
10.1093/annonc/mdz112.
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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 |
| Open access status: | An open access version is available from UCL Discovery |
| 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 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: | https://discovery-pp.ucl.ac.uk/id/eprint/10072350 |
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