Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody
Abstract
Bispecific antibodies (bsAbs) can efficiently mediate tumor cell killing by redirecting preactivated or costimulated T cells to disseminated tumor cells, especially in a minimal residual disease situation. This study demonstrates that the trifunctional bsAb BiLu is able to kill tumor cells very efficiently without any additional costimulation of effector cells in vitro and in vivo. Remarkably, this bsAb also induces a long-lasting protective immunity against the targeted syngeneic mouse tumors (B16 melanoma and A20 B-cell lymphoma, respectively). A strong correlation was observed between the induction of a humoral immune response with tumor-reactive antibodies and the survival of mice. This humoral response was at least in part tumor specific as shown in the A20 model by the detection of induced anti-idiotype antibodies. Both the survival of mice and antitumor titers were significantly diminished when F(ab′)2 fragments of the same bsAb were applied, demonstrating the importance of the Fc region in this process. With the use of T-cell depletion, a contribution of a cellular antitumor response could be demonstrated. These results reveal the necessity of the Fc region of the bsAb with its potent immunoglobulin subclass combination mouse immunoglobulin G2a (IgG2a) and rat IgG2b. The antigen-presenting system seems to be crucial for achieving an efficient tumor cell killing and induction of long-lasting antitumor immunity. Hereby, the recruitment and activation of accessory cells by the intact bsAb is essential.
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In animal studies, 100% of mice administered an injection of 4 μg of triomabs survived after intraperitoneal injection of a lethal dose of EpCAM+ melanoma cells.
“In animal studies, 100% of mice administered an injection of 4 μg of triomabs survived after intraperitoneal (IP) injection of a lethal dose of EpCAM + melanoma cells. 25”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [25]
All mice rechallenged on day 144 after the primary challenge were still able to reject the tumor, indicating high efficacy and long duration of the antitumor response.
“All mice rechallenged on day 144 after the primary challenge were still able to reject the tumor, indicating the high efficacy and long duration of the antitumor response.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [25]
The antitumor effect was dependent on the presence of the hybrid Fc and involved a humoral response directed against non-transfected (EPCAM-) tumor cells.
“This effect was dependent on the presence of the hybrid Fc, and involved a humoral response directed against the non-transfected (EPCAM -) tumor cells.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [25]
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- Authors
- Ruf, P., & Lindhofer, H.
- Affiliations
- Helmholtz Munich (DE)
- ORCID
- Ruf, Peter
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2001-10-15
- Volume
- 98
- Issue
- 8
- Pages
- 2526-2534
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1972848082
- Cited by
- 174
- References
- 34
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 11 · 2015: 9 · 2014: 15 · 2013: 9 · 2012: 16
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- 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, trifunctional antibody, antitumor immunity, Fc fragment, humoral immune response, anti-idiotypic antibodies, T cell depletion, antigen-presenting cells, B16 melanoma, tumor cell killing, immunoglobulin G2a, tumor-specific antibodies
- MeSH terms
- Animals, Antibodies, Neoplasm, Antibody Formation, Antibody Specificity, Cytotoxicity, Immunologic, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunoglobulin G, Immunoglobulin Idiotypes, Immunoglobulin Fab Fragments, Immunoglobulin Fc Fragments, Melanoma, Experimental, Mice, Inbred BALB C, Mice, Inbred C57BL, Survival Rate, Antibodies, Bispecific, Mice, Rats
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