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Updated: May 20, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Recognition based hormonal 95kDa monoclonal antibody on three human cancer cell lines for developing targeted
Guru Pad Bandopadhyaya1, Geetanjali Arora, Jaya Shukla
1Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India. guru47@gmail.com
Abstract:
The present study aimed to explore the possibility of developing a immuno-imaging/therapeutic agent for hCG-expressing tumors by using antibodies raised against them. Three human cancer cell lines were selected:lung adenocarcinoma (A549), glioblastoma (U87MG) and breast cancer (MCF7). Anti-β-hCG monoclonal antibody, obtained from ascitic fluid, was purified by affinity chromatography followed by characterization and titration. Ectopic expression of hCG on these cell lines was tested by flow cytometry and in-vitro cytotoxicity with antibodies was tested by MTT assay on the cell line with the highest percentage binding. For positive and negative controls, immortalized trophoblast cells (SW71) and peripheral blood monocytes were used. Antibody was then radiolabeled with lutetium-177 ((177)Lu) and in vivo biodistribution studies were conducted in murine tumor model. Antibodies could be purified to homogeneity with a concentration 28mg/mL. Percentage receptor expression on A549, U87MG and MCF7 cells was 95%, 66% and 55% respectively. About 90% of A549 cells could be killed with antibody at 72h post-treatment. No cytotoxicity was observed on SW71 despite a high binding percentage (96%). Antibodies were radiolabeled with high efficiency (∼98%). In-vivo studies using radiolabeled antibodies showed hepato-biliary excretion route and significant uptake in A549 tumor. In conclusion, among the 3 cancer cell lines, lung adenocarcinoma significantly expresses β-hCG and shows dose dependent cytotoxicity with anti-β-hCG antibody. Radiolabeling of this antibody can aid in imaging and also has the potential of enhancing its therapeutic potential. This study provides a platform for further studies for targeted radio-immuno imaging and subsequent therapy of hCG-expressing cancers.
Insights
Researchers developed an anti-beta-human chorionic gonadotropin antibody for imaging and therapy of hCG-expressing tumors. Lung adenocarcinoma cells showed significant beta-hCG expression and dose-dependent cytotoxicity, indicating potential for targeted radio-immuno imaging and therapy.
Area of Science:
- Oncology
- Immunology
- Radiochemistry
Background:
- Human chorionic gonadotropin (hCG) is ectopically expressed in various cancers, presenting a potential therapeutic target.
- Development of targeted immunoconjugates requires specific antibodies against tumor-associated antigens like beta-hCG (β-hCG).
- Radio-immunotherapy combines the specificity of antibodies with the cytotoxic effects of radionuclides for targeted cancer treatment.
Purpose of the Study:
- To investigate the potential of developing an immuno-imaging and therapeutic agent targeting hCG-expressing tumors.
- To evaluate the efficacy of a purified anti-β-hCG monoclonal antibody in vitro and in vivo.
- To explore the feasibility of radiolabeling the antibody for targeted radio-immuno imaging and therapy.
Main Methods:
- Purification and characterization of anti-β-hCG monoclonal antibody from ascitic fluid.
- Assessment of ectopic β-hCG expression on lung adenocarcinoma (A549), glioblastoma (U87MG), and breast cancer (MCF7) cell lines using flow cytometry.
- In vitro cytotoxicity assays (MTT) and in vivo biodistribution studies in a murine tumor model using 177Lu-radiolabeled antibody.
Main Results:
- Purified anti-β-hCG antibody showed high specificity, with A549 cells exhibiting the highest β-hCG expression (95%).
- In vitro studies demonstrated significant dose-dependent cytotoxicity (90% cell death at 72h) against A549 cells.
- In vivo studies confirmed successful radiolabeling (∼98% efficiency) and significant uptake in A549 tumors with hepato-biliary excretion.
Conclusions:
- Lung adenocarcinoma (A549) cells significantly express β-hCG, making them a suitable target for anti-β-hCG antibody-based therapies.
- The radiolabeled anti-β-hCG antibody demonstrates potential for both diagnostic imaging and therapeutic applications in hCG-expressing cancers.
- This study provides a foundation for developing targeted radio-immuno imaging and therapy strategies for specific cancer types.
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