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

Zhaoming Wang; Chaobo Yin; Lawrence G Lum; Andrean Simons; George J Weiner

doi:10.1186/s13045-021-01216-w

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

Journal article

Open access

Peer reviewed

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

Zhaoming Wang, Chaobo Yin, Lawrence G Lum, Andrean Simons and George J Weiner

Journal of hematology and oncology, Vol.14(1), pp.204-204

12/09/2021

DOI: 10.1186/s13045-021-01216-w

PMCID: PMC8656063

PMID: 34886888

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https://doi.org/10.1186/s13045-021-01216-wView

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Abstract

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.

Antibodies, Bispecific - pharmacology

Antibody-Dependent Cell Cytotoxicity - drug effects

Antineoplastic Agents, Immunological - pharmacology

Cells, Cultured

Humans

Killer Cells, Natural - drug effects

Killer Cells, Natural - immunology

Lymphocyte Activation - drug effects

T-Lymphocytes - immunology

Details

Title: Subtitle: Bispecific antibody-activated T cells enhance NK cell-mediated antibody-dependent cellular cytotoxicity
Creators: Zhaoming Wang - University of Iowa
Chaobo Yin - University of Iowa
Lawrence G Lum - University of Virginia
Andrean Simons - University of Iowa
George J Weiner - University of Iowa
Resource Type: Journal article
Publication Details: Journal of hematology and oncology, Vol.14(1), pp.204-204
DOI: 10.1186/s13045-021-01216-w
PMID: 34886888
PMCID: PMC8656063
NLM abbreviation: J Hematol Oncol
ISSN: 1756-8722
eISSN: 1756-8722
Grant note: P30 CA86862 / NCI NIH HHS P50 CA97274 / NCI NIH HHS R01 CA182526 / NCI NIH HHS
Language: English
Date published: 12/09/2021
Academic Unit: Oral Pathology, Radiology and Medicine; Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9984359694502771

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