Abstract
Mounting an immune response sufficient to eradicate a tumor is the goal of modern immunotherapy. Single agent therapies with checkpoint inhibitors or costimulatory molecule agonists are effective only for a...
Highlights
To elaborate on our previous studies, we tested the effect of combination aOX40/aCTLA-4 therapy on antigen-specific T cell expansion and the kinetics of this response
To determine whether CTLA-4 expression on CD8 T cells was required for the efficacy of combination therapy, we used transgenic mice in which the extracellular portion of the mouse CTLA-4 receptor is swapped with the human version, rendering them unresponsive to anti-mouse CTLA-4 antagonism [17]
Our recent studies suggest that finding appropriate vaccination methods to combine with checkpoint inhibitors and costimulatory molecule agonism will be more effective at reducing tumor burden and improving survival than any single agent
Summary
Immunotherapy is quickly garnering attention and enthusiasm as some patients with metastatic disease have achieved long-term remission. Combinations of immunotherapies and/or targeted therapies will be needed to achieve complete tumor regression for a larger portion of patients. OX40 is costimulatory molecule expressed by both CD4 and CD8 T cells following T cell receptor (TCR) ligation [1]. Preclinical data demonstrate that treatment with agonist. Linch and Redmond Journal for ImmunoTherapy of Cancer (2016) 4:31 demonstrated that mice defective in cross-presentation have impaired tumor rejection and that in cancer, DC function is frequently impaired [15, 16]. We hypothesized that vaccination targeting a tumor-associated antigen toward crosspresenting dendritic cells (aDEC-205/HER2 with poly (I: C)) combined with aOX40/aCTLA-4 immunotherapy would promote a robust effector CD8 T cell response capable of clearing established tumors
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