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1366 B7-H3xCD3 bispecific antibody as novel treatment option in HER2-negative breast cancer
  1. Martina S Lutz1,
  2. Laura Weßling2,
  3. Latifa Zekri1,2,
  4. Christian M Tegeler2,
  5. Ilona Hagelstein1,2,
  6. Gundram Jung1 and
  7. Helmut R Salih1,2
  1. 1Eberhard Karls University, Tuebingen, Baden-Wuerttemberg, Germany
  2. 2University Hospital Tuebingen, Tuebingen, Baden-Wuerttemberg, Germany
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Invasive breast cancer is the most common malignant disease in women worldwide. HER2-targeting antibodies like Trastuzumab have achieved notable success in treatment of HER2-positive breast cancer, whereas antibody-based treatment options for HER2-negative patients remain quite limited. B7-H3 (CD276) is overexpressed in various tumor entities on both tumor cells and tumor vessels, the latter facilitating improved infiltration of immune effector cells into the tumor site upon therapeutic targeting. In this study, we investigated the potential of a novel B7-H3xCD3 bispecific antibody termed CC-3 as a therapeutic strategy for HER2-negative breast cancer.

Methods The efficacy of CC-3 in treatment of HER2-negative breast cancer was evaluated using various in vitro assays including analysis of T cell activation, proliferation, cytokine release and tumor cell lysis.

Results Our analysis revealed a high expression of B7-H3 on various breast cancer cell lines, regardless of the molecular subtype. Functional analysis using HER2-negative breast cancer cell lines demonstrated that CC-3 induces profound T cell activation and secretion of IL-2, IFNg as well as TNF, and most importantly potent tumor cell lysis. Moreover, CC-3 induced strong T cell proliferation and formation of T cell memory subsets.

Conclusions These promising results highlight the therapeutic potential of CC-3 for treatment of HER2-negative breast cancer.

Ethics Approval The studies involving human participants were reviewed and approved by IRB (ethics committee of the Faculty of Medicine of the Eberhard Karls Universität Tübingen) at the University Hospital Tübingen and was conducted in accordance with the Declaration of Helsinki; reference number13/2007V.

Consent Human material was collected after obtaining informed consent. The patients/participants provided their written informed consent to participate in this study.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

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