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https://hdl.handle.net/2440/90689
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Type: | Journal article |
Title: | Lymphodepletion is permissive to the development of spontaneous T-cell responses to the self-antigen PR1 early after allogeneic stem cell transplantation and in patients with acute myeloid leukemia undergoing WT1 peptide vaccination following chemotherapy |
Author: | Rezvani, K. Yong, A. Mielke, S. Savani, B. Jafarpour, B. Eniafe, R. Le, R. Musse, L. Boss, C. Childs, R. John Barrett, A. |
Citation: | Cancer Immunology Immunotherapy, 2012; 61(7):1125-1136 |
Publisher: | Springer Verlag |
Issue Date: | 2012 |
ISSN: | 0340-7004 1432-0851 |
Statement of Responsibility: | Katayoun Rezvani, Agnes S. M. Yong, Stephan Mielke, Bipin N. Savani, Behnam Jafarpour, Rhoda Eniafe, Robert Quan Le, Laura Musse, Carole Boss, Richard Childs, A. John Barrett |
Abstract: | PR1, an HLA-A*0201 epitope shared by proteinase-3 (PR3) and elastase (ELA2) proteins, is expressed in normal neutrophils and overexpressed in myeloid leukemias. PR1-specific T cells have been linked to graft-versus-leukemia (GVL) effect. We hypothesized that lymphopenia induced by chemo-radiotherapy can enhance weak autoimmune responses to self-antigens such as PR1. We measured PR1-specific responses in 27 patients 30–120 days following allogeneic stem cell transplant (SCT) and correlated these with ELA2 and PR3 expression and minimal residual disease (MRD). Post-SCT 10/13 CML, 6/9 ALL, and 4/5 solid tumor patients had PR1 responses correlating with PR3 and ELA2 expression. At day 180 post-SCT, 8/8 CML patients with PR1 responses were BCR-ABL-negative compared with 2/5 BCR-ABL-positive patients (P = 0.025). In contrast, PR1 responses were detected in 2/4 MRD-negative compared with 4/5 MRD-positive ALL patients (P = 0.76). To assess whether the lymphopenic milieu also exaggerates weak T-cell responses in the autologous setting, we measured spontaneous induction of PR1 responses in 3 AML patients vaccinated with WT1-126 peptide following lymphodepletion. In addition to WT1-specific T cells, we detected PR1-specific T cells in 2 patients during hematopoietic recovery. Our findings suggest that lymphopenia induced by chemo-radiotherapy enhances weak autoimmune responses to self-antigens, which may result in GVL if the leukemia expresses the relevant self-antigen. |
Keywords: | PR1; WT1; Vaccine; Lymphopenia-driven homeostasis; Leukemia; Immunotherapy |
Rights: | © Springer-Verlag (outside the USA) 2011 |
DOI: | 10.1007/s00262-011-1187-z |
Published version: | http://dx.doi.org/10.1007/s00262-011-1187-z |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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