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Direct detection and quantitation of a distinct T-cell epitope derived from tumor-specific epithelial cell-associated mucin using human recombinant antibodies endowed with the antigen-specific, major histocompatibility complex-restricted specificity of T cells.
Cancer Res 2002; 62(20):5835-44CR

Abstract

The recent characterization of MHC-displayed tumor-associated antigens that recognize effector cells of the immune system has created new perspectives for cancer therapy. Antibodies that recognize these tumor-associated MHC-peptide complexes with the same specificity as the T-cell antigen receptor will therefore be valuable tools for immunotherapy, as well as for studying antigen presentation in human cancers. Most tumor-associated antigens are expressed in only one or a few tumor types; however, specific T-cell epitopes derived from the Mucin-1 tumor-associated antigen (MUC1) that are widely expressed in many cancers were identified and shown to be recognized by CTLs. We selected a large nonimmune repertoire of phage Fab antibodies on recombinant human class I HLA-A2 complexes displaying an antigenic T-cell epitope derived from MUC1. High frequency of anti-MHC-peptide binders was observed (84%), and surprisingly, a high percentage (80%) of antibodies was fully specific for the MUC1 epitope. We isolated a surprisingly large panel of 16 different high-affinity human recombinant Fab antibodies that exhibited peptide-specific, MHC-restricted binding characteristics of T cells. The analyzed Fabs not only recognize the cognate MHC-peptide complex in a recombinant soluble form but also the native complex as displayed on the surface of antigen-presenting cells and breast tumor cells. Therefore, these findings demonstrate the ability to transform the unique fine specificity but low intrinsic affinity of T-cell receptors on T cells into high-affinity soluble antibody molecules endowed with a T-cell antigen receptor-like specificity. These molecules may prove to be very important and widely applicable for monitoring the expression of specific MHC-peptide complexes on the surface of tumor and immune cells for structure-function studies of T-cell receptor-peptide-MHC interactions, as well as for developing new targeting agents for immunotherapy.

Authors+Show Affiliations

Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12384546

Citation

Cohen, Cyril J., et al. "Direct Detection and Quantitation of a Distinct T-cell Epitope Derived From Tumor-specific Epithelial Cell-associated Mucin Using Human Recombinant Antibodies Endowed With the Antigen-specific, Major Histocompatibility Complex-restricted Specificity of T Cells." Cancer Research, vol. 62, no. 20, 2002, pp. 5835-44.
Cohen CJ, Hoffmann N, Farago M, et al. Direct detection and quantitation of a distinct T-cell epitope derived from tumor-specific epithelial cell-associated mucin using human recombinant antibodies endowed with the antigen-specific, major histocompatibility complex-restricted specificity of T cells. Cancer Res. 2002;62(20):5835-44.
Cohen, C. J., Hoffmann, N., Farago, M., Hoogenboom, H. R., Eisenbach, L., & Reiter, Y. (2002). Direct detection and quantitation of a distinct T-cell epitope derived from tumor-specific epithelial cell-associated mucin using human recombinant antibodies endowed with the antigen-specific, major histocompatibility complex-restricted specificity of T cells. Cancer Research, 62(20), pp. 5835-44.
Cohen CJ, et al. Direct Detection and Quantitation of a Distinct T-cell Epitope Derived From Tumor-specific Epithelial Cell-associated Mucin Using Human Recombinant Antibodies Endowed With the Antigen-specific, Major Histocompatibility Complex-restricted Specificity of T Cells. Cancer Res. 2002 Oct 15;62(20):5835-44. PubMed PMID: 12384546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct detection and quantitation of a distinct T-cell epitope derived from tumor-specific epithelial cell-associated mucin using human recombinant antibodies endowed with the antigen-specific, major histocompatibility complex-restricted specificity of T cells. AU - Cohen,Cyril J, AU - Hoffmann,Noa, AU - Farago,Marganit, AU - Hoogenboom,Hennie R, AU - Eisenbach,Lea, AU - Reiter,Yoram, PY - 2002/10/18/pubmed PY - 2002/11/30/medline PY - 2002/10/18/entrez SP - 5835 EP - 44 JF - Cancer research JO - Cancer Res. VL - 62 IS - 20 N2 - The recent characterization of MHC-displayed tumor-associated antigens that recognize effector cells of the immune system has created new perspectives for cancer therapy. Antibodies that recognize these tumor-associated MHC-peptide complexes with the same specificity as the T-cell antigen receptor will therefore be valuable tools for immunotherapy, as well as for studying antigen presentation in human cancers. Most tumor-associated antigens are expressed in only one or a few tumor types; however, specific T-cell epitopes derived from the Mucin-1 tumor-associated antigen (MUC1) that are widely expressed in many cancers were identified and shown to be recognized by CTLs. We selected a large nonimmune repertoire of phage Fab antibodies on recombinant human class I HLA-A2 complexes displaying an antigenic T-cell epitope derived from MUC1. High frequency of anti-MHC-peptide binders was observed (84%), and surprisingly, a high percentage (80%) of antibodies was fully specific for the MUC1 epitope. We isolated a surprisingly large panel of 16 different high-affinity human recombinant Fab antibodies that exhibited peptide-specific, MHC-restricted binding characteristics of T cells. The analyzed Fabs not only recognize the cognate MHC-peptide complex in a recombinant soluble form but also the native complex as displayed on the surface of antigen-presenting cells and breast tumor cells. Therefore, these findings demonstrate the ability to transform the unique fine specificity but low intrinsic affinity of T-cell receptors on T cells into high-affinity soluble antibody molecules endowed with a T-cell antigen receptor-like specificity. These molecules may prove to be very important and widely applicable for monitoring the expression of specific MHC-peptide complexes on the surface of tumor and immune cells for structure-function studies of T-cell receptor-peptide-MHC interactions, as well as for developing new targeting agents for immunotherapy. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/12384546/Direct_detection_and_quantitation_of_a_distinct_T_cell_epitope_derived_from_tumor_specific_epithelial_cell_associated_mucin_using_human_recombinant_antibodies_endowed_with_the_antigen_specific_major_histocompatibility_complex_restricted_specificity_of_T_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12384546 DB - PRIME DP - Unbound Medicine ER -