CTLA-4 blockade augments human T lymphocyte-mediated suppression of lung tumor xenografts in SCID mice
| Autor: | Fang-An Chen, Stephen D. Hess, Richard B. Bankert, Michael S. Sabel, Thomas F. Conway, Nejat K. Egilmez |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Immunoconjugates Lung Neoplasms T-Lymphocytes medicine.medical_treatment Mice SCID Lymphocyte Activation Mice Antigens Ly Immunology and Allergy CTLA-4 Antigen Membrane Glycoproteins biology Antibodies Monoclonal CD28 hemic and immune systems Killer Cells Natural Oncology Antigens Surface B7-1 Antigen Carcinoma Squamous Cell Antibody NK Cell Lectin-Like Receptor Subfamily B medicine.drug_class Transplantation Heterologous Immunology chemical and pharmacologic phenomena Monoclonal antibody Abatacept Immune system CD28 Antigens Antigens CD medicine Animals Humans Lectins C-Type Antigens business.industry Proteins Dendritic Cells Immunotherapy Antigens Differentiation Fusion protein Blockade CTLA-4 biology.protein Severe Combined Immunodeficiency B7-2 Antigen business |
| Zdroj: | Cancer Immunology, Immunotherapy. 54:944-952 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-005-0668-3 |
| Popis: | Previous studies by others using transplantable murine tumor models have demonstrated that the administration of antibodies that block CTLA-4 interaction with B7 can provoke the elimination of established tumors, and that the tumor suppression is mediated by T-cells and/or cells expressing NK1.1. Studies from our lab have established in a human/severe combined immunodeficient (SCID) mouse chimeric model that autologous peripheral blood leukocytes (PBL) can suppress the growth of tumor xenografts in a PBL dose-dependent fashion, and that this suppression is dependent upon the patient's T and NK cells. Using this human/mouse chimeric model, we sought to determine whether an antibody blockade of CTLA-4 would enhance the anti-tumor response of a patient's PBL. It was first important to determine whether the tumor suppression observed in the SCID model was dependent upon CD28/B7 co-stimulation. Blockade of B7 with a human CTLA-4-Ig fusion protein completely abrogated the lymphocyte-mediated tumor suppression, confirming in this model that tumor suppression is dependent upon a CD28/B7 co-stimulation. Using two different CTLA-4 specific monoclonal antibodies, we observed that CTLA-4 blockade significantly enhanced the human lymphocyte-mediated tumor suppression in mice co-engrafted with PBL and tumor cells. This enhancement was observed in both an allogeneic setting (in which the PBL were allogeneic with respect to the tumor) and an autologous setting (in which the PBL and tumor were from the same patient). These results sustain the notion that human anti-tumor immune response can be augmented (in vivo) by blocking the interaction between CTLA-4 and B7. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink