title: Angiogenic cytokines are antibody targets during graft-versus-leukemia reactions.
abstract: OBJECTIVE
  The graft-versus-leukemia (GVL) reaction is an important example of immune-mediated tumor destruction. A coordinated humoral and cellular response accomplishes leukemia cell killing, but the specific targets remain largely uncharacterized. To learn more about the antigens that elicit antibodies during GVL reactions, we analyzed patients with advanced myelodysplasia (MDS) and acute myelogenous leukemia (AML) who received an autologous, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cell vaccine early after allogeneic hematopoietic stem cell transplantation (HSCT).
  
  
  METHODS
  A combination of tumor-derived cDNA expression library screening, protein microarrays, and antigen-specific ELISAs were used to characterize sera obtained longitudinally from 15 patients with AML/MDS who were vaccinated early after allogeneic HSCT.
  
  
  RESULTS
  A broad, therapy-induced antibody response was uncovered, which primarily targeted intracellular proteins that function in growth, transcription/translation, metabolism, and homeostasis. Unexpectedly, antibodies were also elicited against eight secreted angiogenic cytokines that play critical roles in leukemogenesis. Antibodies to the angiogenic cytokines were evident early after therapy, and in some patients manifested a diversification in reactivity over time. Patients that developed antibodies to multiple angiogenic cytokines showed prolonged remission and survival.
  
  
  CONCLUSIONS
  These results reveal a potent humoral response during GVL reactions induced with vaccination early after allogeneic HSCT and raise the possibility that antibodies, in conjunction with natural killer cells and T lymphocytes, may contribute to immune-mediated control of myeloid leukemias.
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Matthias
authors.initials: M
authors.lastname: Piesche
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Haesook
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Yukoh
authors.initials: Y
authors.lastname: Nakazaki
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: Nehil
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Nasser K
authors.initials: NK
authors.lastname: Yaghi
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Kolodin
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Weiser
authors.affiliation: Translational Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.affiliation: Translational Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Kiefel
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Christine
authors.initials: C
authors.lastname: Canning
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.affiliation: Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. glenn_dranoff@dfci.harvard.edu.
authors.forename: Glenn
authors.initials: G
authors.lastname: Dranoff
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000276:immunology*; D000906:Antibodies / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D015723:Gene Library; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000276:immunology / Q000628:therapy; D008137:Longitudinal Studies; D063868:Patient Outcome Assessment; D015203:Reproducibility of Results; D013997:Time Factors; D014184:Transplantation, Homologous / Q000401:mortality
chemical_list: D043925:Angiogenesis Inducing Agents; D000906:Antibodies; D019496:Cancer Vaccines; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor