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Immune Checkpoint Proteins: A New Therapeutic Paradigm for Cancer—Preclinical Background: CTLA-4 and PD-1 Blockade by Jeffrey Weber is a Medicine article available to read on EtoBox.

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Much of the recent excitement in the translational field of tumor immunology and immunotherapy has been generated by the recognition that immune checkpoint proteins can be blocked by human antibodies with profound effects in vitro, in animal tumor systems, and in patients. Promising clinical data have already been generated in melanoma and other tumor types with human antibodies directed against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1). The preclinical data that supported the clinical development of these two antibodies will be discussed in detail in this review, showing that many of the therapeutic effects of these two agents were predicted by the animal models, as were the immune-related side effects noted with these drugs. In contrast, much of the early work with anti-CTLA-4 antibodies indicated that it had a potent therapeutic effect only when combined with granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced tumor vaccines, and that the antibody alone was effective only in the most immunogenic tumor models in mice. Intriguingly, in patients, the drug alone clearly has had important therapeutic effects, but the addition of vaccines

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Author

Jeffrey Weber

Publisher

Elsevier BV

Published

2010

Language

EN

Field

Medicine (Health Sciences)