Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the Internalization
Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. The bispecific targeting could improve the specificity, affinity, and internalization of the ADC molecules. Prolactin preceptor (PRLR) and HER2 have crosstalk signaling in breast cancer, an...
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| Format: | Article |
| Language: | English |
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Georg Thieme Verlag KG
2022-06-01
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| Series: | Pharmaceutical Fronts |
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| Online Access: | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0042-1749334 |
| _version_ | 1828851119444459520 |
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| author | Hui-Fang Zong Bao-Hong Zhang Jian-Wei Zhu |
| author_facet | Hui-Fang Zong Bao-Hong Zhang Jian-Wei Zhu |
| author_sort | Hui-Fang Zong |
| collection | DOAJ |
| description | Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. The bispecific targeting could improve the specificity, affinity, and internalization of the ADC molecules. Prolactin preceptor (PRLR) and HER2 have crosstalk signaling in breast cancer, and PRLR undergoes a rapid internalization compared with HER2. To improve the efficacy of HER2 ADCs with enhancing the target specificity and internalization, we constructed a PRLR/HER2-targeting bispecific ADC (BsADC). We evaluated the characterization of PRLR × HER2 BsADC from the affinity and internalization, and further assessed its in vitro cytotoxicity in human breast-cancer cell lines (BT474, T47D, and MDA-MB-231) using Cell Count Kit-8 analysis. Our data demonstrated that PRLR × HER2 BsADC kept the affinity to two targeting antigens after conjugating drugs and exhibited higher internalization efficiency in comparison to HER2 ADC. Furthermore, PRLR × HER2 BsADC demonstrated to have superior antitumor activity in human breast cancer in vitro. In conclusion, our findings indicate that it is feasible through increasing the internalization of target antibody to enhance the antitumor activity and therapeutic potential that could be further evaluated in in vivo animal model. |
| first_indexed | 2024-12-12T23:25:40Z |
| format | Article |
| id | doaj.art-1bebf652dae7475d97fde4cd35641eae |
| institution | Directory Open Access Journal |
| issn | 2628-5088 2628-5096 |
| language | English |
| last_indexed | 2024-12-12T23:25:40Z |
| publishDate | 2022-06-01 |
| publisher | Georg Thieme Verlag KG |
| record_format | Article |
| series | Pharmaceutical Fronts |
| spelling | doaj.art-1bebf652dae7475d97fde4cd35641eae2022-12-22T00:08:05ZengGeorg Thieme Verlag KGPharmaceutical Fronts2628-50882628-50962022-06-010402e113e12010.1055/s-0042-1749334Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the InternalizationHui-Fang Zong0Bao-Hong Zhang1Jian-Wei Zhu2Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaEngineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaEngineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaAntibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. The bispecific targeting could improve the specificity, affinity, and internalization of the ADC molecules. Prolactin preceptor (PRLR) and HER2 have crosstalk signaling in breast cancer, and PRLR undergoes a rapid internalization compared with HER2. To improve the efficacy of HER2 ADCs with enhancing the target specificity and internalization, we constructed a PRLR/HER2-targeting bispecific ADC (BsADC). We evaluated the characterization of PRLR × HER2 BsADC from the affinity and internalization, and further assessed its in vitro cytotoxicity in human breast-cancer cell lines (BT474, T47D, and MDA-MB-231) using Cell Count Kit-8 analysis. Our data demonstrated that PRLR × HER2 BsADC kept the affinity to two targeting antigens after conjugating drugs and exhibited higher internalization efficiency in comparison to HER2 ADC. Furthermore, PRLR × HER2 BsADC demonstrated to have superior antitumor activity in human breast cancer in vitro. In conclusion, our findings indicate that it is feasible through increasing the internalization of target antibody to enhance the antitumor activity and therapeutic potential that could be further evaluated in in vivo animal model.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0042-1749334bispecific adcprlrher2internalizationantitumor |
| spellingShingle | Hui-Fang Zong Bao-Hong Zhang Jian-Wei Zhu Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the Internalization Pharmaceutical Fronts bispecific adc prlr her2 internalization antitumor |
| title | Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the Internalization |
| title_full | Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the Internalization |
| title_fullStr | Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the Internalization |
| title_full_unstemmed | Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the Internalization |
| title_short | Generating a Bispecific Antibody Drug Conjugate Targeting PRLR and HER2 with Improving the Internalization |
| title_sort | generating a bispecific antibody drug conjugate targeting prlr and her2 with improving the internalization |
| topic | bispecific adc prlr her2 internalization antitumor |
| url | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0042-1749334 |
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