Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment



Turaj, Anna H, Hussain, Khiyam, Cox, Kerry L, Rose-Zerilli, Matthew JJ, Testa, James, Dahal, Lekh N, Chan, HT Claude, James, Sonya, Field, Vikki L, Carter, Matthew J
et al (show 12 more authors) (2017) Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment. CANCER CELL, 32 (6). 777 - 791.

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Abstract

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.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 24 Jun 2020 10:42
Last Modified: 30 Nov 2020 13:10
DOI: 10.1016/j.ccell.2017.11.001
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3091469