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Selection of tumor-specific internalizing human antibodies from phage libraries
M A Poul1, B Becerril, U B Nielsen
1Departments of Anesthesia and Pharmaceutical Chemistry, University of California, San Francisco, Rm. 3C-38, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA, 94110, USA.
Journal of Molecular Biology
|September 1, 2000
Summary
Researchers developed a method to select tumor-targeting, internalizing antibodies from phage libraries. These antibodies can deliver therapeutics into cells and some exhibit direct anti-cancer effects, demonstrating a novel approach for targeted cancer therapy.
Area of Science:
- Biotechnology
- Molecular Biology
- Oncology
Background:
- Antibody internalization is crucial for targeted therapeutics like immunotoxins and antibody-drug conjugates.
- Developing tumor-specific internalizing antibodies is essential for effective targeted cancer therapy.
Purpose of the Study:
- To generate tumor-specific internalizing antibodies directly from a phage antibody library.
- To evaluate the therapeutic potential of selected internalizing antibodies.
Main Methods:
- A non-immune single-chain variable fragment (scFv) phage antibody library was panned on the SKBR3 breast tumor cell line.
- Internalized phage were recovered and used for subsequent rounds of selection.
- Selected scFv were analyzed for binding specificity, internalization efficiency, and functional effects.
Main Results:
- 40% of selected clones specifically bound tumor cells (SKBR3) without binding normal human cells.
- Two scFv (F5, C1) targeted ErbB2, and one (H7) targeted the transferrin receptor.
- F5 and H7 scFv were efficiently internalized and demonstrated functional effects, including downstream signaling and growth inhibition.
Conclusions:
- Direct selection of internalizing, receptor-specific antibodies from phage libraries using cell panning is feasible.
- These antibodies can be utilized to deliver various molecules into cells for therapeutic purposes.
- Selected antibodies can possess direct therapeutic effects, such as inhibiting tumor cell growth.