Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood.

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Presentation transcript:

Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation Jenny Zilberberg, Rena Feinman, Robert Korngold Biology of Blood and Marrow Transplantation Volume 21, Issue 6, Pages 1000-1007 (June 2015) DOI: 10.1016/j.bbmt.2014.11.001 Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Schematic representation of a forward immunology method for the identification of miHA as tumor targets. Panel (A-1): Identification and expansion of T cell clone with strong GVT/GVHD reactivity. Panel (A-2): The reactive T cell clone is then scanned against a cDNA library with EBV-LCL from CEPH families to identify the cDNA clone eliciting cytotoxic activity. Genetic linkage analysis is performed on this cDNA clone to identify genes encoding the potential tumor miHA. Panel (B): Preparation of cDNA library from patient-derived tumor cells or from EBV-LCL from CEPH families. Current methods for the production and expansion of T cell clones are discussed in more detail in the “Production of bulk T cells as a tool for discovery of TAA” section of this review. Biology of Blood and Marrow Transplantation 2015 21, 1000-1007DOI: (10.1016/j.bbmt.2014.11.001) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Schematic representation of reversed immunological methods to determine miHA peptides. Steps for determining and validating miHA epitopes eliciting relevant antitumor T cell activity are depicted in this figure. A first phase of computational prediction determines a number of putative epitopes, which are then confirmed experimentally for their capacity to induce an in vivo T cell response. Biology of Blood and Marrow Transplantation 2015 21, 1000-1007DOI: (10.1016/j.bbmt.2014.11.001) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions