Details

Autor(en) / Beteiligte

• Biernacki, Melinda A.
• Marina, Ovidiu
• Zhang, Wandi
• Liu, Fenglong
• Bruns, Ingmar
• Cai, Ann
• Neuberg, Donna
• Canning, Christine M.
• Alyea, Edwin P.
• Soiffer, Robert J.
• Brusic, Vladimir
• Ritz, Jerome
• Wu, Catherine J.

Titel

Antigen targets of remission-inducing immune therapy are expressed on CML progenitor cells

Ist Teil von

• Cancer research (Chicago, Ill.), 2010-01, Vol.70 (3), p.906-915

Erscheinungsjahr

2010

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The curative effect of existing graft-versus-leukemia (GvL)-based therapies such as donor lymphocyte infusion (DLI) for chronic myeloid leukemia (CML) may result from immunologic targeting of self-renewing CML progenitor cells. Patients who achieved durable remission following DLI developed a significant B cell lymphocytosis after treatment, which was not observed in patients unresponsive to DLI. To identify targets of this B cell response, we probed two complementary immunoproteomic platforms, a bacteriophage expression library and a high-density protein microarray, using plasma immunoglobulin from seven CML patients with clinically apparent GvL and without graft-versus-host disease after DLI. In total, 62 antigens elicited greater reactivity from post-DLI versus pre-DLI plasma. More than 70% of the antigens were detectable in CML CD34+ cells in an analysis of HG-FOCUS and HG-U133A Affymetrix microarrays, suggesting that expression in malignant progenitor cells is a feature common to antibody targets of DLI. Higher transcript and protein expression in CML compared to normal CD34+ cells was confirmed for three target antigens (RAB38, TBCE, and DUSP12). Together, they consistently elicited antibody responses in an additional 18 of 21 CML patients with clinical responses to therapy, but not in normal donors and only rarely in patients without CML. Immunologic targets of curative DLI responses thus comprise multiple CML progenitor cell-expressed antigens that may represent potential immunogens for vaccination and/or monitoring of immunotherapeutic strategies designed to eliminate myeloid leukemia stem cells.