TY - JOUR
T1 - Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality
AU - Holtan, Shernan G.
AU - Savid-Frontera, Constanza
AU - Walton, Kelly
AU - Eaton, Anne A.
AU - Demorest, Connor
AU - Hoeschen, Andrea
AU - Zhang, Ling
AU - Reid, Kayla
AU - Kurian, Tony
AU - Sayegh, Zena
AU - Julia, Estefania
AU - Maakaron, Joseph
AU - Bachanova, Veronika
AU - El Jurdi, Najla
AU - MacMillan, Margaret L.
AU - Weisdorf, Daniel J.
AU - Felices, Martin
AU - Miller, Jeffrey S.
AU - Blazar, Bruce R.
AU - Davila, Marco L.
AU - Betts, Brian C.
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/3/15
Y1 - 2023/3/15
N2 - Purpose: Acute and chronic GVHD remain major causes of transplant-related morbidity and mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). We have shown CD83 chimeric antigen receptor (CAR) T cells prevent GVHD and kill myeloid leukemia cell lines. In this pilot study, we investigate CD83 expression on GVHD effector cells, correlate these discoveries with clinical outcomes, and evaluate critical therapeutic implications for transplant recipients. Experimental Design: CD83 expression was evaluated among circulating CD4+ T cells, B-cell subsets, T follicular helper (Tfh) cells, and monocytes from patients with/without acute or chronic GVHD (n = 48 for each group), respectively. CD83 expression was correlated with survival, TRM, and relapse after alloHCT. Differential effects of GVHD therapies on CD83 expression was determined. Results: CD83 overexpression on CD4+ T cells correlates with reduced survival and increased TRM. Increased CD83+ B cells and Tfh cells, but not monocytes, are associated with poor posttransplant survival. CD83 CAR T eliminate autoreactive CD83+ B cells isolated from patients with chronic GVHD, without B-cell aplasia as observed with CD19 CAR T. We demonstrate robust CD83 antigen density on human acute myeloid leukemia (AML), and confirm potent antileukemic activity of CD83 CAR T in vivo, without observed myeloablation. Conclusions: CD83 is a promising diagnostic marker of GVHD and warrants further investigation as a therapeutic target of both GVHD and AML relapse after alloHCT.
AB - Purpose: Acute and chronic GVHD remain major causes of transplant-related morbidity and mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). We have shown CD83 chimeric antigen receptor (CAR) T cells prevent GVHD and kill myeloid leukemia cell lines. In this pilot study, we investigate CD83 expression on GVHD effector cells, correlate these discoveries with clinical outcomes, and evaluate critical therapeutic implications for transplant recipients. Experimental Design: CD83 expression was evaluated among circulating CD4+ T cells, B-cell subsets, T follicular helper (Tfh) cells, and monocytes from patients with/without acute or chronic GVHD (n = 48 for each group), respectively. CD83 expression was correlated with survival, TRM, and relapse after alloHCT. Differential effects of GVHD therapies on CD83 expression was determined. Results: CD83 overexpression on CD4+ T cells correlates with reduced survival and increased TRM. Increased CD83+ B cells and Tfh cells, but not monocytes, are associated with poor posttransplant survival. CD83 CAR T eliminate autoreactive CD83+ B cells isolated from patients with chronic GVHD, without B-cell aplasia as observed with CD19 CAR T. We demonstrate robust CD83 antigen density on human acute myeloid leukemia (AML), and confirm potent antileukemic activity of CD83 CAR T in vivo, without observed myeloablation. Conclusions: CD83 is a promising diagnostic marker of GVHD and warrants further investigation as a therapeutic target of both GVHD and AML relapse after alloHCT.
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U2 - 10.1158/1078-0432.CCR-22-2837
DO - 10.1158/1078-0432.CCR-22-2837
M3 - Article
C2 - 36622700
AN - SCOPUS:85150226003
SN - 1078-0432
VL - 29
SP - 1114
EP - 1124
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 6
ER -