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Published on: September 25, 2018
Monoclonal antibody targeting of human non-small cell carcinoma of the lung
R Stein1, R M Sharkey, D M Goldenberg
1Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Abstract:
Murine monoclonal antibody RS5-4H6 is an IgG1, which was raised against a crude membrane preparation of Calu-3, a human adenocarcinoma of the lung cell line. MAb RS5-4H6 reacts with the majority (14 of 15) of surgical specimens of non-small cell carcinomas of the lung by immunoperoxidase staining. Reactivity with this antibody was not limited to tumors of the lung but rather exhibited pancarcinoma reactivity, staining 87% of tumors from all organs tested. In this study we examined the potential of radiolabeled RS5-4H6 to target Calu-3 xenografts in nude mice. The monoclonal antibody was found to localize preferentially to the heterotransplanted tumors, with 6.6% of the injected dose/g accreting in the tumor at 7 days, a 3-fold higher level than an anti-carcinoembryonic antigen monoclonal antibody which was used as a negative control.
Insights
Monoclonal antibody RS5-4H6 shows pancarcinoma reactivity, effectively targeting lung cancer xenografts. Radiolabeled RS5-4H6 preferentially accumulates in tumors, demonstrating its potential for cancer imaging and therapy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Murine monoclonal antibody RS5-4H6 (MAb RS5-4H6) is an IgG1 developed against human lung adenocarcinoma cells (Calu-3).
- MAb RS5-4H6 demonstrates broad reactivity, staining 87% of diverse human tumor types and 14 of 15 non-small cell lung carcinoma specimens.
Purpose of the Study:
- To evaluate the tumor-targeting potential of radiolabeled MAb RS5-4H6 in vivo.
- To assess the antibody's biodistribution and preferential accumulation in Calu-3 xenografts.
Main Methods:
- Calu-3 human lung adenocarcinoma xenografts were established in nude mice.
- Radiolabeled MAb RS5-4H6 was administered, and its accretion in tumors was measured at 7 days post-injection.
- An anti-carcinoembryonic antigen monoclonal antibody served as a negative control.
Main Results:
- Radiolabeled RS5-4H6 demonstrated preferential localization to Calu-3 xenografts.
- Tumor accretion reached 6.6% of injected dose per gram at 7 days.
- This level was 3-fold higher compared to the control antibody.
Conclusions:
- MAb RS5-4H6 exhibits pancarcinoma reactivity and effectively targets lung cancer xenografts.
- The preferential accumulation of radiolabeled RS5-4H6 in tumors suggests its potential as a diagnostic or therapeutic agent for various cancers.
