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Identification of anti-CD16a single domain antibodies and their application in bispecific antibodies
Yining Zhao1,2, Yumei Li1,2, Xiaoqiong Wu1,2
1School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Abstract:
CD16a (FcγRIIIa) mediates the antibody dependent cellular cytotoxicity (ADCC) and is important for anti-tumor activities of many therapeutic antibodies. Bispecific antibody targeting natural killer (NK) cells has been studied for cancer therapy. In this work, anti-CD16a single-domain antibodies were identified from hCD16a immunized camel. Bispecific antibodies are then constructed by fusing these single domain antibodies with an anti-CEA single domain antibody. These bispecific antibodies can recruite NK cells to kill CEA-positive tumor cells, and inhibit tumor growth in vivo, suggesting that these anti-CD16a single domain antibodies are powerful tools to engaging NK cells for cancer therapy.
Insights
Researchers developed novel bispecific antibodies by fusing anti-CD16a single-domain antibodies with anti-CEA antibodies. These engineered antibodies effectively recruit natural killer (NK) cells to eliminate cancer cells and inhibit tumor growth.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- CD16a (FcγRIIIa) is crucial for antibody-dependent cellular cytotoxicity (ADCC) and the efficacy of therapeutic antibodies against tumors.
- Bispecific antibodies designed to target natural killer (NK) cells represent a promising strategy in cancer therapy.
Purpose of the Study:
- To identify and characterize anti-CD16a single-domain antibodies from immunized camels.
- To construct bispecific antibodies by combining anti-CD16a single-domain antibodies with anti-CEA single-domain antibodies.
- To evaluate the efficacy of these bispecific antibodies in recruiting NK cells to kill CEA-positive tumor cells and inhibiting tumor growth in vivo.
Main Methods:
- Immunization of camels with human CD16a (hCD16a).
- Isolation and identification of anti-CD16a single-domain antibodies.
- Construction of bispecific antibodies by fusing anti-CD16a and anti-CEA single-domain antibodies.
- In vitro and in vivo assessment of NK cell recruitment and anti-tumor activity.
Main Results:
- Novel anti-CD16a single-domain antibodies were successfully identified.
- Constructed bispecific antibodies demonstrated the ability to recruit NK cells towards CEA-positive tumor cells.
- Significant inhibition of tumor growth was observed in vivo, highlighting the therapeutic potential.
Conclusions:
- The identified anti-CD16a single-domain antibodies are effective tools for engaging NK cells in cancer therapy.
- Bispecific antibodies leveraging these single-domain antibodies show promise for targeting CEA-positive tumors.
- This approach offers a powerful strategy for enhancing anti-tumor immunity through NK cell activation.
