| Autor: |
Shernan G. Holtan, Constanza Savid-Frontera, Kelly Walton, Anne A. Eaton, Connor Demorest, Andrea Hoeschen, Ling Zhang, Kayla Reid, Tony Kurian, Zena Sayegh, Estefania Julia, Joseph Maakaron, Veronika Bachanova, Najla El Jurdi, Margaret L. MacMillan, Daniel J. Weisdorf, Martin Felices, Jeffrey S. Miller, Bruce R. Blazar, Marco L. Davila, Brian C. Betts |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Clinical cancer research : an official journal of the American Association for Cancer Research. |
| ISSN: |
1557-3265 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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