On-target restoration of a split T cell-engaging antibody for precision immunotherapy

Banaszek A, Bumm TGP, Nowotny B, Geis M, Jacob K, Woelfl M, Trebing J, Kucka K, Kouhestani D, Gogishvili T, Krenz B, Lutz J, Rasche L, Hoenemann D, Neuweiler H, Heiby JC, Bargou RC, Wajant H, Einsele H, Riethmueller G, Stuhler G (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 10

Article Number: 5387

Journal Issue: 1

DOI: 10.1038/s41467-019-13196-0

Abstract

T cell-engaging immunotherapies are changing the landscape of current cancer care. However, suitable target antigens are scarce, restricting these strategies to very few tumor types. Here, we report on a T cell-engaging antibody derivative that comes in two complementary halves and addresses antigen combinations instead of single molecules. Each half, now coined hemibody, contains an antigen-specific single-chain variable fragment (scFv) fused to either the variable light (VL) or variable heavy (VH) chain domain of an anti-CD3 antibody. When the two hemibodies simultaneously bind their respective antigens on a single cell, they align and reconstitute the original CD3-binding site to engage T cells. Employing preclinical models for aggressive leukemia and breast cancer, we show that by the combinatorial nature of this approach, T lymphocytes exclusively eliminate dual antigen-positive cells while sparing single positive bystanders. This allows for precision targeting of cancers not amenable to current immunotherapies.

Involved external institutions

Universitätsklinikum Würzburg DE Germany (DE) Julius-Maximilians-Universität Würzburg DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Banaszek, A., Bumm, T.G.P., Nowotny, B., Geis, M., Jacob, K., Woelfl, M.,... Stuhler, G. (2019). On-target restoration of a split T cell-engaging antibody for precision immunotherapy. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-13196-0

MLA:

Banaszek, Agnes, et al. "On-target restoration of a split T cell-engaging antibody for precision immunotherapy." Nature Communications 10.1 (2019).

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