The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients

Friedrich, Mirco; Neri, Paola; Kehl, Niklas; Michel, Julius; Steiger, Simon; Kilian, Michael; Leblay, Noémie; Maity, Ranjan; Sankowski, Roman; Lee, Holly; Barakat, Elie; Ahn, Sungwoo; Weinhold, Niels; Rippe, Karsten; Bunse, Lukas; Platten, Michael; Goldschmidt, Hartmut; Müller‐Tidow, Carsten; Raab, Marc‐Steffen; Bahlis, Nizar J.

doi:10.1016/j.ccell.2023.02.008

articleCancer CellMar 9, 2023HYBRID OA

The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients

MFMirco Friedrich PNPaola Neri NKNiklas Kehl JMJulius Michel SSSimon Steiger

Broad Institute · Heidelberg University · +10 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical response. We find the abundance of exhausted-like CD8+ T cell clones to be associated with clinical response failure, and…

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Topics & keywords

Topics

Keywords

CD8
Major histocompatibility complex
Immunotherapy
Multiple myeloma
Immune system
MHC class I
Immunology
T cell

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