The new face of bispecific antibodies: targeting cancer and much more
Open accessAbstract
The term magic bullet was first coined by bacteriologist Paul Ehrlich in the late 1800s to describe a chemical with the ability to specifically target microorganisms while sparing normal host cells. His concept was later expanded to include treatments for cancer, but it is only in recent decades, with development and improvements in monoclonal antibody (mAb) technology, that the full therapeutic implications of "magic bullet" strategies have been realized. Expanding on the success of mAb-targeting, linking the specificity of two mAbs into a single agent, called a bispecific antibody (BiAb), allows for targeting of a therapeutic biological agent or cell to specific tissue antigens. Classically, BiAbs have been used for several decades to redirect cytotoxic T cells or other effector cells to kill tumor cells. Here, we review preclinical models and ongoing phase I clinical trials in which arming polyclonally activated T cells with BiAbs may provide anti-tumor activity without dose-limiting toxicities. Additionally, we review findings from this novel strategy that merges magic bullet technology with hematopoietic stem cells to repair injured myocardium. Arming stem cells with BiAbs directed at injury-associated antigens enhances specific homing and engraftment to myocardial infarctions and may significantly improve cardiac function, strongly suggesting new paradigms for BiAb-targeting applications in tissue repair.
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The PACT approach avoids direct systemic injection of bispecific antibody in the patient, thereby significantly minimizing toxicity associated with free murine Fc bearing molecules.
“This approach has the advantage of avoiding a direct systemic injection of bsAb in the patient, thereby significantly minimizing toxicity associated with free murine Fc bearing molecules. 19”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [19]
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Bispecific antibodies for cancer therapy: The light at the end of the tunnel?
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- Authors
- Lum, L. G., Davol, P. A., & Lee, R. J.
- Affiliations
- Boston University (US)
- Roger Williams Medical Center (US)
- University of California, San Francisco (US)
- Corresponding author
- Lum, Lawrence G.
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 34
- Issue
- 1
- Pages
- 1-6
- ISSN
- 0301-472X (ISSN-L)
- OpenAlex
- W2003723481
- Cited by
- 32
- References
- 73
- Citations by year
- 2021: 1 · 2018: 1 · 2016: 2 · 2015: 3 · 2012: 3
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Experimental Hematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA092344, R01 CA 92344)
- National Center for Research Resources (P20RR018757, 5P20RR18757)
- 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 › Toxin Mechanisms and Immunotoxins
- Keywords
- bispecific antibodies, magic bullet, monoclonal antibodies, adoptive T cell therapy, T cell redirection, cancer immunotherapy, hematopoietic stem cell therapy, myocardial infarction, cardiac repair, stem cell homing, tissue-specific antigens
- MeSH terms
- Clinical Trials as Topic, Humans, Immunotherapy, Lymphocyte Activation, Myocardial Infarction, Neoplasms, T-Lymphocytes, Antibodies, Bispecific, Hematopoietic Stem Cell Transplantation, Antigens, CD34
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