ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Generation and preclinical characterization of a novel bispecific CD19-TCRgammadelta antibody for the treatment of B cell acute lymphoblastic leukemia
Provisionally accepted
Joseph Kauer1,2,3*
Fabian Vogt2Sebastian Hörner2Valentin Schmidt3Carsten Müller-Tidow3Simon Raffel3
Helmut Salih1,2,4Gundram Jung2Martin Pflügler2*- 1German Cancer Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany
- 2Eberhard Karls Universitat Tubingen, Tübingen, Germany
- 3UniversitatsKlinikum Heidelberg, Heidelberg, Germany
- 4Universitatsklinikum Tubingen, Tübingen, Germany
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B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the clonal expansion of immature lymphoblastic cells. Treating patients with disease relapse is challenging, especially after allogeneic stem cell transplantation (aSCT). Although the CD19xCD3 bispecific antibody (bsAb) blinatumomab has improved outcomes for patients with relapsed B-ALL, T cell exhaustion and immune-associated treatment side effects remain problematic. Vγ9Vδ2 T cells constitute a relatively small subset in healthy individuals but their abundance increases after aSCT, and higher numbers correlate with improved outcomes. Unlike αβ T cells, Vγ9Vδ2 T cells are not allo-reactive, do not contribute to graft-versus-host disease and release fewer inflammatory cytokines. Using hybridoma technology, we here generated a panel of hybridoma-derived monoclonal antibodies directed against the Vγ9Vδ2 receptor that specifically activate Vγ9Vδ2 T cells. Subsequently, we generated an IgG-based recombinant CD19xγδ bsAb to activate Vγ9Vδ2 T cells. Our bsAb potently induces Vγ9Vδ2 T cell activation, proliferation, lysis of B-ALL cell lines in vitro in a dose-dependent manner. Additionally, the bsAb mediates lysis of primary leukemic blasts of patients ex vivo and depletion of CD19-positive target cells in an autologous setting. No significant αβ T cell activation or proliferation was observed. In summary, the selective activation of Vγ9δ2 T cells using our novel CD19xγδ bsAb constitutes a This is a provisional file, not the final typeset article. promising immunotherapeutic approach for the treatment of B-ALL. Our results warrant further clinical evaluation especially in patients with minimal residual disease after aSCT or CD3-directed bsAb therapy.
Keywords: Acute Lymphoblastic Leukemia, bispecific antibodies, CD19, gammadelta T cells, Immunotherapy
Received: 20 Oct 2025; Accepted: 10 Feb 2026.
Copyright: © 2026 Kauer, Vogt, Hörner, Schmidt, Müller-Tidow, Raffel, Salih, Jung and Pflügler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Joseph Kauer
Martin Pflügler
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