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Single-cell cytotoxicity with radiolabeled antibodies.
G L Ong1, S E Elsamra, D M Goldenberg
1Garden State Cancer Center, Belleville, New Jersey 07109, USA.
Summary
Targeting cell surface antigens with radiolabeled antibodies effectively kills cancer cells. This study shows cell surface delivery is potent, unlike lysosomal delivery, for potent radioimmunotherapy against B-lymphoma.
Area of Science:
- Immunology
- Oncology
- Radiochemistry
Background:
- Previous studies showed radiolabeled anti-CD74 effectively killed Raji B-lymphoma cells via high uptake and lysosomal accumulation of the radionuclide.
- Antibody (Ab) catabolism in lysosomes leads to radionuclide accumulation, crucial for anti-CD74 efficacy.
Purpose of the Study:
- To compare the efficacy of radioactivity delivered to the cell surface versus the cytoplasm.
- To investigate antibodies targeting cell surface antigens like major histocompatibility complex class II and CD20.
Main Methods:
- Conjugating 111In, 125I, and 131I to anti-major histocompatibility complex class II and anti-CD20 antibodies.
- Comparing the cytotoxic effects of these radiolabeled antibodies on B-lymphoma cells.
- Monitoring radionuclide uptake and estimating radiation dose delivered.
Main Results:
- 111In-labeled anti-major histocompatibility complex class II and anti-CD20 antibodies demonstrated high, specific killing of B-lymphoma cells (100% kill).
- These antibodies, remaining on the cell surface, were effective with non-residualizing labels (125I, 131I), unlike anti-CD74 which required a residualizing label.
- Cytotoxicity correlated with the estimated radiation dose delivered to the cells.
Conclusions:
- Radioimmunotherapy targeting cell surface antigens is effective without requiring residualizing radiolabels.
- Antibody localization (cell surface vs. cytoplasm) significantly impacts radioimmunotherapy efficacy.
- This approach holds promise for treating various B-lymphoma and potentially other cancers with lower-density antigens.