Abstract
Vidutolimod, also known as CMP-001, is a virus-like particle composed of the Qβ bacteriophage coat protein encasing a TLR9 agonist. Vidutolimod injected intratumorally is showing promise in early phase clinical trials based on its ability to alter the tumor microenvironment and induce an anti-tumor immune response. We previously demonstrated that the in vivo efficacy of vidutolimod is dependent on the presence of anti-Qβ antibodies that enhance opsonization and uptake of vidutolimod by TLR9-expressing plasmacytoid dendritic cells (pDCs). Here, we evaluated the effect of immune complexes, including anti-Qβ-coated vidutolimod, on induction of Type 1 Interferon production by peripheral blood mononuclear cells in response to vidutolimod and soluble TLR9 agonists. Immune complexes, including but not limited to anti-Qβ-coated vidutolimod, indirectly suppressed TLR9-mediated Type 1 Interferon production by pDCs in a monocyte-dependent manner. These findings indicate that anti-Qβ-coated vidutolimod has effects in addition to those mediated by TLR9 that could have important clinical implications for understanding the mechanism of action of this exciting new approach to in situ immunization and cancer immunotherapy.
Highlights
The field of cancer immunotherapy has progressed rapidly over the last decade
B cells obtained from the peripheral blood mononuclear cells (PBMCs) of a subject participating in a clinical trial of vidutolimod [4] were transformed with EBV into lymphoblasts and used to produce monoclonal and polyclonal human anti-Qβ antibodies
We previously reported that uptake of antibody-coated vidutolimod by monocytes is significantly higher than that of plasmacytoid dendritic cells (pDCs) even though pDC uptake is responsible for the resulting production of Type I Interferon [3]
Summary
The field of cancer immunotherapy has progressed rapidly over the last decade. A key component of this progress has been greater understanding of the cross-talk in the tumor microenvironment (TME) between malignant and benign cells. This has led to major advances in the treatment of cancer. The most impactful of these has been use of agents that block immune checkpoints, such as pembrolizumab. Despite this major success, most patients still fail to benefit from immune checkpoint blockade therapy.
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