1. Tumor Cell Retention of Antibody Fab Fragments Is Enhanced by an Attached HIV TAT Protein-Derived Peptide
- Author
-
E. Nichols, D. C. Anderson, M. Barry, D. Woodle, Alan R. Fritzberg, and R. Manger
- Subjects
Time Factors ,media_common.quotation_subject ,Molecular Sequence Data ,Cell ,Biophysics ,Enzyme-Linked Immunosorbent Assay ,Peptide ,Biology ,Biochemistry ,Iodine Radioisotopes ,Immunoglobulin Fab Fragments ,Tumor Cells, Cultured ,medicine ,Humans ,Amino Acid Sequence ,Carbon Radioisotopes ,Internalization ,Melanoma ,Molecular Biology ,Peptide sequence ,Binding selectivity ,media_common ,chemistry.chemical_classification ,Cell Membrane ,HIV ,Biological Transport ,Chloroquine ,Cell Biology ,Molecular biology ,Peptide Fragments ,In vitro ,Kinetics ,medicine.anatomical_structure ,chemistry ,Colonic Neoplasms ,Gene Products, tat ,biology.protein ,tat Gene Products, Human Immunodeficiency Virus ,Antibody ,Conjugate - Abstract
Two peptide analogs of the 37-62 sequence region of the HIV TAT protein bind tightly to the surface of A431 breast carcinoma cells. After conjugation to either of two poorly internalized anti-tumor antibody Fab fragments, the analogs enhanced the in vitro cell surface retention and internalization of the Fab fragments to the level of the whole antibodies. This was at the expense of some binding specificity in the case of 1.6 peptides/NRLU-10 Fab, but not in the case of 1.1 peptides/Fab. Enhanced retention may occur by enhanced bivalent binding of the Fab fragments. The internalized fraction of free peptide, but not of the Fab conjugates, is enhanced by chloroquine. The conjugates which were less specific for tumor cell binding may be useful for enhanced retention/internalization of specifically acting agents, for use at specific sites of injection, or against pre-separated target cell populations, while the more specific conjugate may be of interest for further development.
- Published
- 1993