Graft-versus-Leukemia Antigen CML66 Elicits Coordinated B-Cell and T-Cell Immunity after Donor Lymphocyte Infusion

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BlankGraft-versus-Leukemia Antigen CML66 Elicits Coordinated B-Cell and T-Cell

Immunity after Donor Lymphocyte Infusion

1.. Wandi Zhang1,

2.. Jaewon Choi1,

3.. Wanyong Zeng1,

4.. Shelby A. 2,

5.. Edwin P. Alyea2,4,

6.. G. Rheinwald3,

7.. M. Canning2,

8.. Vladimir Brusic1,

9.. Tetsuro Sasada1,2,4,

10.. Ellis L. Reinherz1,2,4,

11.. Jerome Ritz1,2,4,

12.. J. Soiffer2,4, and

13.. J. Wu1,2,4

+ Author Affiliations

1.. Authors' Affiliations:1Cancer Vaccine Center and 2Department of Medical

Oncology, Dana-Farber Cancer Institute; 3Department of Dermatology, Brigham and

Women's Hospital and Harvard Skin Disease Research Center, Harvard Medical

School; 4Department of Medicine, Brigham and Women's Hospital, Harvard Medical

School, Boston, Massachusetts

1.. Corresponding Author:

J. Wu, Dana-Farber Cancer Institute, Harvard Institutes of Medicine,

Room 416B, 77 Avenue Louis Pasteur, Boston, MA 02115. Phone: 617-632-5943; Fax:

617-632-3351; E-mail: cwu@....

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. Clin Cancer Res; 16(10); 2729–39. ©2010 AACR.

Footnotes

a.. Note: Supplementary data for this article are available at Clinical Cancer

Research Online (http://clincancerres.aacrjournals.org/).

b.. W. Zhang and J. Choi are equal contributors.