Isolation of native human monoclonal autoantibodies to breast cancer.
Using a unique fusion partner cell line, MFP-2, and B-lymphocytes from breast cancer patients, we developed a set of fully human monoclonal antibodies (MAbs) that bind with high specificity and sensitivity to breast cancer cells. Immunofluorescent staining of normal tissues, primary tumors, and metastatic lymph nodes demonstrates that these antibodies are specific for breast cancer of autologous and allogeneic origin. We have also determined that many of the antibodies selected based on specific binding to breast cancer cells and tissue also bind prostate cancer cells and tissue with high specificity and sensitivity. The targets of these antibodies have been localized to the cytoplasm and membrane. Biological assays for internalization and cytotoxicity demonstrated the ability of three antibodies to rapidly internalize. Our study demonstrates that isolation of native human MAbs from the natural antibody repertoire, targeted to cancer cells, is feasible and may provide a source of tools for immunotherapy.
Kirman
Irena
I
Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Kalantarov
Gary F
GF
Lobel
Leslie I
LI
Hibshoosh
Hanina
H
Estabrook
Alison
A
Canfield
Robert
R
Trakht
Ilya
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification*; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification*; D001943:Breast Neoplasms / Q000276:immunology*; D002459:Cell Fusion; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies