Journal
CANCER CELL
Volume 32, Issue 6, Pages 777-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2017.11.001
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Funding
- Cancer Research UK [C30010/A15269]
- Kay Kendall Leukaemia Fund [KKL 584]
- Wessex Medical Research Innovation Fund [2011 R06, 2014 U10]
- Leuka Charity
- John Goldman Fellowship [2016/JGF/0003]
- Southampton CRUK Centre Development Fund
- Celldex Therapeutics
- MRC [MC_PC_15078] Funding Source: UKRI
- Cancer Research UK [20537, 15269, 19502, 21621] Funding Source: researchfish
- Medical Research Council [MC_PC_15078] Funding Source: researchfish
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Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8(+) T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation. This study demonstrates the therapeutic advantage of using an immunomodulatory mAb to regulate lymphoid cells, which then recruit and activate myeloid cells for enhanced killing of mAb-opsonized tumors.
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