Protein disulfide isomerases are antibody targets during immune-mediated tumor destruction
| Autor: | Robert J. Soiffer, Jerome Ritz, Daniel J. DeAngelo, Donna Neuberg, Vincent T. Ho, Richard Stone, Matthew Vanneman, Masahisa Jinushi, Glenn Dranoff, Catia Fonseca |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
medicine.drug_class
Immunology Protein Disulfide-Isomerases Major histocompatibility complex Monoclonal antibody Biochemistry Cancer Vaccines Mice Immune system Antigen Antigens CD Antigens Neoplasm Cell Line Tumor medicine Cytotoxic T cell Animals Humans CTLA-4 Antigen Protein disulfide-isomerase Carcinoma Renal Cell Immunobiology Bone Marrow Transplantation Gene Library Mice Inbred BALB C biology Histocompatibility Antigens Class I Antibodies Monoclonal Granulocyte-Macrophage Colony-Stimulating Factor Cell Biology Hematology Kidney Neoplasms Leukemia Myeloid biology.protein Cancer research Female Antibody Clone (B-cell biology) |
| Popis: | The identification of cancer antigens that contribute to transformation and are linked with immune-mediated tumor destruction is an important goal for immunotherapy. Toward this end, we screened a murine renal cell carcinoma cDNA expression library with sera from mice vaccinated with irradiated tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor (GM-CSF). Multiple nonmutated, overexpressed proteins that function in tumor cell migration, protein/nucleic acid homeostasis, metabolism, and stress responses were detected. Among these, the most frequently recognized clone was protein disulfide isomerase (PDI). High titer antibodies to human PDI were similarly induced in an acute myeloid leukemia patient who achieved a complete response after vac-cination with irradiated, autologous GM-CSF–secreting tumor cells in the setting of nonmyeloablative allogeneic bone marrow transplantation. Moreover, ERp5, a closely related disulfide isomerase involved in major histocompatibility complex (MHC) class I chain-related protein A (MICA) shedding, also evoked potent humoral reactions in diverse solid and hematologic malignancy patients who responded to GM-CSF–secreting tumor cell vaccines or antibody blockade of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4). Together, these findings reveal the unexpected immunogenicity of PDIs and raise the possibility that these gene products might serve as targets for therapeutic monoclonal antibodies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|