Simultaneous Activation of T Cells and Accessory Cells by a New Class of Intact Bispecific Antibody Results in Efficient Tumor Cell Killing
Open accessAbstract
Bispecific Abs (bsAb) are promising immunological tools for the elimination of tumor cells in minimal residual disease situations. In principle, they target an Ag on tumor cells and recruit one class of effector cell. Because immune reactions in vivo are more complex and are mediated by different classes of effector cell, we argue that conventional bsAb might not yield optimal immune responses at the tumor site. We therefore constructed a bsAb that combines the two potent effector subclasses mouse IgG2a and rat IgG2b. This bispecific molecule not only recruits T cells via its one binding arm, but simultaneously activates FcγR+ accessory cells via its Fc region. We demonstrate here that the activation of both T lymphocytes and accessory cells leads to production of immunomodulating cytokines like IL-1β, IL-2, IL-6, IL-12, and DC-CK1. Thus this new class of bsAb elicits excellent antitumor activity in vitro even without the addition of exogenous IL-2, and therefore represents a totally self-supporting system.
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An anti-CD3 x anti-EpCAM bispecific antibody created with this approach was capable of binding target cells and human T cells, activating dendritic cells, inducing NK-dependent ADCC, and stimulating tumor cell phagocytosis by macrophages.
“The investigators used this approach to create an anti-CD3 x anti-EpCAM bsAb, and demonstrated that this antibody was capable of binding to target cells and human T cells, but was also capable of activating dendritic cells (DC), inducing NK-dependent ADCC and stimulating tumor cell phagocytosis by macrophages. 22,23”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [23]
The hybrid rat/mouse Fc portion efficiently interacted with activating human Fc receptors FcγRI and FcγRIII, but not with inhibitory FcγRIIB.
“Surprisingly, the resulting hybrid rat/mouse Fc portion efficiently interacted with activating human Fc receptors (FcγRI and FcγRIII), but not inhibitory ones (FcγRIIB), thereby reaching the goal that other groups had hoped to achieve using human Fc engineering. 22,23”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [23]
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Self-citation
- Authors
- Zeidler, R., Reisbach, G., Wollenberg, B., Lang, S., Chaubal, S., Schmitt, B., & Lindhofer, H.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Helmholtz Munich (DE)
- Clinical Cooperation Group “Bispecific Antibodies,” Department of Otorhinolaryngology, Ludwig-Maximilians-University , Munich ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-08-01
- Volume
- 163
- Issue
- 3
- Pages
- 1246-1252
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1492340933
- Cited by
- 204
- References
- 37
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 8 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 8 · 2016: 4 · 2015: 9 · 2014: 15 · 2013: 13 · 2012: 18
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Journal of Immunology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- bispecific antibodies, T cell activation, Fc gamma receptor, accessory cells, tumor cell killing, minimal residual disease, cytokine production, IL-12, IL-1β, interleukin-6, interleukin-2, anticancer activity
- MeSH terms
- Epithelial Cell Adhesion Molecule, Animals, Antibody-Dependent Cell Cytotoxicity, Antigen-Presenting Cells, Antigens, Neoplasm, Antineoplastic Agents, Cells, Cultured, Dendritic Cells, Humans, Interleukin-2, Lymphocyte Activation, Recombinant Fusion Proteins, T-Lymphocytes, Tumor Cells, Cultured, Cell Adhesion Molecules, Cytokines, Antibodies, Bispecific, Coculture Techniques, Mice, Rats
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