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Clin Cancer Res. 2010 May 15;16(10):2729-39. doi: 10.1158/1078-0432.CCR-10-0415. Epub 2010 May 11.

Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion.

Author information

1
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.

Abstract

PURPOSE:

The target antigens of graft-versus-leukemia that are tumor associated are incompletely characterized.

EXPERIMENTAL DESIGN:

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.

PMID:
20460482
PMCID:
PMC2872105
DOI:
10.1158/1078-0432.CCR-10-0415
[Indexed for MEDLINE]
Free PMC Article

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