Serologic markers of effective tumor immunity against chronic lymphocytic leukemia include nonmutated B-cell antigens.

Cancer Research
Ovidiu MarinaCatherine J Wu

Abstract

Patients with chronic lymphocytic leukemia (CLL) who relapse after allogeneic transplant may achieve durable remission following donor lymphocyte infusion (DLI), showing the potency of donor-derived immunity in eradicating tumors. We sought to elucidate the antigenic basis of the effective graft-versus-leukemia (GvL) responses associated with DLI for the treatment of CLL by analyzing the specificity of plasma antibody responses developing in two DLI-treated patients who achieved long-term remission without graft-versus-host disease. By probing high-density protein microarrays with patient plasma, we discovered 35 predominantly intracellular antigens that elicited high-titer antibody reactivity greater in post-DLI than in pre-DLI plasma. Three antigens-C6orf130, MDS032, and ZFYVE19-were identified by both patients. Along with additional candidate antigens DAPK3, SERBP1, and OGFOD1, these proteins showed higher transcript and protein expression in B cells and CLL cells compared with normal peripheral blood mononuclear cells. DAPK3 and the shared antigens do not represent minor histocompatibility antigens, as their sequences are identical in both donor and tumor. Although ZFYVE19, DAPK3, and OGFOD1 elicited minimal antibody reacti...Continue Reading

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Citations

Aug 19, 2011·The Journal of Biological Chemistry·Francis C PetersonBrian F Volkman
Sep 29, 2011·The Cancer Journal·Christopher S Hourigan, Hyam I Levitsky
Aug 6, 2013·The Journal of Clinical Investigation·Ute E BurkhardtCatherine J Wu
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Apr 15, 2017·The Cancer Journal·David A Braun, Catherine J Wu
Jun 24, 2017·Expert Review of Proteomics·Jessica G Duarte, Jonathan M Blackburn

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