Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion.
OBJECTIVE
The target antigens of graft-versus-leukemia that are tumor associated are incompletely characterized.


METHODS
We examined responses developing against CML66, an immunogenic antigen preferentially expressed in myeloid progenitor cells identified from a patient with chronic myelogenous leukemia who attained long-lived remission following CD4+ donor lymphocyte infusion (DLI).


RESULTS
From this patient, CML66-reactive CD8+ T-cell clones were detected against an endogenously presented HLA-B*4403-restricted epitope (HDVDALLW). Neither CML66-specific antibody nor T-cell responses were detectable in peripheral blood before DLI. However, by 1 month after DLI, CD8+ T cells were present in peripheral blood and at 10-fold higher frequency in marrow. Subsequently, plasma antibody to CML66 developed in association with disease remission. Donor-derived CML66-reactive T cells were detected at low levels in vivo in marrow before DLI by ELISpot and by a nested PCR-based assay to detect clonotypic T-cell receptor sequences but not in blood of the patient pre-DLI nor of the graft donor.


CONCLUSIONS
CD4+ DLI results in rapid expansion of preexisting marrow-resident leukemia-specific donor CD8+ T cells, followed by a cascade of antigen-specific immune responses detectable in blood. Our single-antigen analysis thus shows that durable posttransplant tumor immunity is directed in part against nonpolymorphic overexpressed leukemia antigens that elicit coordinated cellular and humoral immunity.
Zhang
Wandi
W
Cancer Vaccine Center and Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Skin Disease Research Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Choi
Jaewon
J
Zeng
Wanyong
W
Rogers
Shelby A
SA
Alyea
Edwin P
EP
Rheinwald
James G
JG
Canning
Christine M
CM
Brusic
Vladimir
V
Sasada
Tetsuro
T
Reinherz
Ellis L
EL
Ritz
Jerome
J
Soiffer
Robert J
RJ
Wu
Catherine J
CJ
D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology; D017710:Lymphocyte Transfusion; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000628:therapy; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; C431278:NUDCD1 protein, human
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