Bispecific antibody-activated T cells enhance NK cell-mediated antibody-dependent cellular cytotoxicity

Journal of Hematology & Oncology

Lawrence G. Lum¹  Zhaoming Wang²  George J. Weiner³  Andrean Simons⁴  Chaobo Yin⁵ 

[1] Division of Hematology/Oncology, Department of Medicine, The University of Virginia, Charlottesville, VA, USA;Holden Comprehensive Cancer Center, University of Iowa, 5970-Z JPP, 200 Hawkins Drive, 52242, Iowa City, IA, USA;Cancer Biology Graduate Program, University of Iowa, Iowa City, IA, USA;Holden Comprehensive Cancer Center, University of Iowa, 5970-Z JPP, 200 Hawkins Drive, 52242, Iowa City, IA, USA;Cancer Biology Graduate Program, University of Iowa, Iowa City, IA, USA;Department of Internal Medicine, University of Iowa, Iowa City, IA, USA;Holden Comprehensive Cancer Center, University of Iowa, 5970-Z JPP, 200 Hawkins Drive, 52242, Iowa City, IA, USA;Cancer Biology Graduate Program, University of Iowa, Iowa City, IA, USA;Department of Pathology, University of Iowa, Iowa City, IA, USA;Holden Comprehensive Cancer Center, University of Iowa, 5970-Z JPP, 200 Hawkins Drive, 52242, Iowa City, IA, USA;Department of Internal Medicine, University of Iowa, Iowa City, IA, USA;

关键词: NK cell;    ADCC;    Anti-CD20;    Blinatumomab;    Bispecific antibody;   

DOI  :  10.1186/s13045-021-01216-w

来源: Springer

【 摘 要 】

Resistance to anti-cancer monoclonal antibody (mAb) therapy remains a clinical challenge. Previous work in our laboratory has shown that T cell help in the form of interleukin-2 maintains long-term NK cell viability and NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Lack of such T cell help may be a potential mechanism for resistance to mAb therapy. Here, we evaluate whether concomitant treatment with anti-CD3 × anti-cancer bispecific antibodies (bsAbs) can overcome this resistance by enhancing T cell help, and thereby maintaining long-term NK cell-mediated ADCC. Normal donor peripheral blood mononuclear cells were depleted of T cells, replenished with defined numbers of autologous T cells (from 0.75 to 50%) and co-cultured with mono-/bispecific antibody-treated target tumor cells for up to 7 days. At low T cell concentrations, bsAb-activated T cells (mainly CD4+ T cells) were more effective than resting T cells at maintaining NK cell viability and ADCC. Brief (4 h to 2 day) bsAb exposure was sufficient to enhance long-term ADCC by NK cells. These findings raise the hypothesis that local T cell activation mediated by systemic treatment with anti-CD3 X anti-cancer bsAb may enhance the anti-tumor efficacy of monospecific mAbs that mediate their primary therapeutic effect via NK-mediated ADCC.

【 授权许可】

CC BY