title: Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity.
abstract: This phase Ib clinical trial evaluated whether pretargeting of CD20(+) clonogenic myeloma precursor cells (CMPCs) with anti-CD3 × anti-CD20 bispecific antibody-armed T cells (BATs) before autologous stem cell transplantation (SCT) in patients with standard-risk and high-risk multiple myeloma would induce antimyeloma immunity that could be detected and boosted after SCT. All 12 patients enrolled in this study received 2 BATs infusions before SCT, and 4 patients received a booster infusion of BATs after SCT. Pretargeting CD138(-)/CD20(+) CMPCs with BATs before SCT was safe and reduced levels of CMPCs by up to 58% in the postinfusion bone marrow in patients who remained in remission. Four of 5 patients who remained in remission had a >5-fold increase in IFN-γ enzyme-linked immunospot responses. SOX2 antibody increased after BATs infusions and persisted after SCT. The median anti-SOX2 level at 3 months after SCT was 28.1 ng/mL (range, 4.6 to 256 ng/mL) in patients who relapsed and 46 ng/mL (range, 28.3 to 73.3 ng/mL) in patients who remained in remission. The immune correlates suggest that infusions of targeted T cells given before SCT were able to reduce CMPC levels and induced cellular and humoral antimyeloma immunity that could be transferred and boosted after SCT.
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan; Department of Medicine, Wayne State University, Detroit, Michigan; Department of Immunology and Microbiology, Wayne State University, Detroit, Michigan. Electronic address: LGL4F@virginia.edu.
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Lum
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan. Electronic address: AT2FX@virginia.edu.
authors.forename: Archana
authors.initials: A
authors.lastname: Thakur
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan.
authors.forename: Sri Vidya
authors.initials: SV
authors.lastname: Kondadasula
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan; Department of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Al-Kadhimi
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Deol
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan.
authors.forename: Elyse N
authors.initials: EN
authors.lastname: Tomaszewski
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yano
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan.
authors.forename: Dana L
authors.initials: DL
authors.lastname: Schalk
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan; Department of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Lois
authors.initials: L
authors.lastname: Ayash
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Zonder
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan; Department of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Uberti
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan; Department of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Muneer H
authors.initials: MH
authors.lastname: Abidi
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan; Department of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Voravit
authors.initials: V
authors.lastname: Ratanatharathorn
mesh_terms: D000328:Adult; D000368:Aged; D018033:Antibodies, Bispecific / Q000008:administration & dosage*; D018951:Antigens, CD20 / Q000276:immunology*; D064592:Autografts; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000276:immunology*; D033581:Stem Cell Transplantation; D053668:Syndecan-1
chemical_list: D018033:Antibodies, Bispecific; D018951:Antigens, CD20; C508241:SDC1 protein, human; D053668:Syndecan-1
keywords: Activated T cells; Bispecific antibodies; Multiple myeloma
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