Tatibody, a recombinant antibody with higher internalization potency.
Amin Ramezani1, Amir Asgari2, Elina Kaviani1
1Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
Molecular Immunology
|May 10, 2021
Summary
Researchers developed Tatibody, a modified pertuzumab antibody, by incorporating the Human Immunodeficiency Virus TAT Protein Transduction Domain (TAT-PTD). This novel antibody drug conjugate candidate demonstrates significantly higher tumor cell internalization, enhancing its potential for cancer treatment.
Area of Science:
- Biotechnology
- Oncology
- Immunology
Background:
- Antibody drug conjugates (ADCs) are effective in tumor cell killing by delivering cytotoxic agents.
- Increasing the internalization rate of ADCs is crucial for improving tumor treatment efficacy.
Purpose of the Study:
- To engineer a novel pertuzumab variant with enhanced internalization for improved ADC development.
- To investigate the potential of incorporating the TAT Protein Transduction Domain (TAT-PTD) into pertuzumab.
Main Methods:
- Computational methods were used to identify optimal insertion sites for TAT-PTD in the pertuzumab antibody heavy chain.
- A recombinant antibody, Tatibody, was produced in CHO-S cells with TAT-PTD at position 130-140.
- Physicochemical properties and biological activities of Tatibody were evaluated and compared to pertuzumab.
Main Results:
- Tatibody exhibited comparable binding affinity to the ErbB2 receptor as pertuzumab.
- Tatibody demonstrated a 3.6-fold higher internalization potency compared to pertuzumab.
- The modified antibody showed potential as a superior candidate for ADC construction.
Conclusions:
- Tatibody represents a promising advancement in ADC technology due to its enhanced internalization.
- This engineered antibody offers a potential strategy for more effective cancer therapy via ADCs.
- Further development of Tatibody could lead to improved therapeutic outcomes in ErbB2-positive cancers.
