Immunotherapy of multiple myeloma.

The Journal of Clinical Investigation
Simone A Minnie, Geoffrey R Hill

Abstract

Multiple myeloma (MM), a bone marrow-resident hematological malignancy of plasma cells, has remained largely incurable despite dramatic improvements in patient outcomes in the era of myeloma-targeted and immunomodulatory agents. It has recently become clear that T cells from MM patients are able to recognize and eliminate myeloma, although this is subverted in the majority of patients who eventually succumb to progressive disease. T cell exhaustion and a suppressive bone marrow microenvironment have been implicated in disease progression, and once these are established, immunotherapy appears largely ineffective. Autologous stem cell transplantation (ASCT) is a standard of care in eligible patients and results in immune effects beyond cytoreduction, including lymphodepletion, T cell priming via immunogenic cell death, and inflammation; all occur within the context of a disrupted bone marrow microenvironment. Recent studies suggest that ASCT reestablishes immune equilibrium and thus represents a logical platform in which to intervene to prevent immune escape. New immunotherapies based on checkpoint inhibition targeting the immune receptor TIGIT and the deletion of suppressive myeloid populations appear attractive, particularly af...Continue Reading

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Citations

Apr 22, 2020·Nature Reviews. Clinical Oncology·Bruce R BlazarWilliam J Murphy
Jun 24, 2020·Leukemia·Nico GagelmannNicolaus Kröger
Nov 21, 2020·Pharmaceuticals·Massimo Offidani, Maria Teresa Petrucci
Feb 16, 2021·Frontiers in Oncology·Leona YamamotoKenneth Carl Anderson
Nov 10, 2020·Frontiers in Endocrinology·Manuel A RiquelmeJean X Jiang
Mar 30, 2021·Frontiers in Immunology·Simone A Minnie, Geoffrey R Hill
Apr 4, 2021·Cancers·Raquel LopesCristina João
Jul 24, 2021·ImmunoTargets and Therapy·Mika Casey, Kyohei Nakamura

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Methods Mentioned

BETA
leukapheresis

Clinical Trials Mentioned

NCT00480363
NCT01169337
NCT02681302
NCT02252263
NCT02654132
NCT02289222
NCT02036502
NCT02726581
NCT02076009
NCT02136134

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