Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies.
Open accessAbstract
Rabbit anti-2,4-dintrophenyl (DNP) antibodies or their F(ab')2 fragments were chemically cross-linked to the anti-mouse Fc gamma R monoclonal antibody 2.4G2 or to its Fab fragment. P388D1 cells were incubated with heteroaggregates between 2.4G2 and anti-DNP (anti-Fc gamma R X anti-DNP) and washed. The resulting cells lysed 2,4,6-trinitrophenyl chicken erythrocytes (TNP CRBC) in a hapten-specific manner. The lysis was inhibited by free hapten but was resistant to inhibition by immune complexes. Other cells coated with antibody heteroaggregates also mediated lysis of TNP-modified target cells. For example, mouse resident peritoneal exudate cells (PEC) lysed TNP CRBC and bacillus Calmette-Guérin-activated PEC lysed both TNP CRBC and TNP tumor targets. Human neutrophils, when incubated with heteroaggregates containing the anti-human neutrophil Fc gamma R antibody 3G8 and anti-DNP also lysed TNP CRBC and TNP-modified tumor cells. To test whether linkage to Fc gamma R was required for lysis, F(ab')2 fragments from the anti-KdDd monoclonal antibody 34-1-2 were cross-linked to anti-DNP F(ab')2 fragments. P388D1 cells (which express Kd and Dd) were then incubated with these heteroaggregates and washed, and their abilities to form conjugates and lyse TNP CRBC were compared with those of P388D1 cells treated with anti-Fc gamma R X anti-DNP. In both cases, P388D1 cells formed conjugates. However, only the cells treated with anti-Fc gamma R X anti-DNP mediated lysis to a significant extent. We conclude that heteroaggregates containing anti-Fc gamma R and anti-target cell antibodies can be used to create potent effector cells against red cell and tumor targets and that bridging of effectors with target cells directly to Fc gamma R on effector cells is required for lysis.
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The potential of using bispecific antibodies to retarget effector cells toward tumor cells was demonstrated in the 1980s.
“The potential of using bispecific antibodies to retarget effector cells toward tumor cells was demonstrated in the 1980s 3,6,7”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [6]
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- Authors
- Karpovsky, B., Titus, J. A., Stephany, D. A., & Segal, D. M.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Titus, J A
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1984-12-01
- Volume
- 160
- Issue
- 6
- Pages
- 1686-1701
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2187539
- OpenAlex
- W2028697515
- Cited by
- 162
- References
- 37
- Citations by year
- 2024: 4 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 3
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Keywords
- heteroaggregates, Fc gamma receptor, effector cells, antibody cross-linking, antibody-mediated cell lysis, P388D1 cells, peritoneal exudate cells, neutrophils, tumor cell lysis, immune complexes
- MeSH terms
- Animals, Antibodies, Antibody-Dependent Cell Cytotoxicity, Antigen-Antibody Complex, Chickens, Dinitrophenols, HLA Antigens, Immunoglobulin Fab Fragments, Killer Cells, Natural, Leukemia P388, Rabbits, Receptors, Fc, Receptors, IgG, 2,4-Dinitrophenol
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