title: Targeting intracellular oncoproteins with antibody therapy or vaccination.
abstract: Antibody-based therapies have better specificity and thus improved efficacy over standard chemotherapy regimens, which result in extended survival and improved quality of life for cancer patients. Because antibodies are viewed as too large to access intracellular locations, antibody therapy has traditionally targeted extracellular or secreted proteins expressed by cancer cells. However, many oncogenic proteins are found within the cell (such as intracellular phosphatases/kinases and transcription factors) and have therefore not been pursued for antibody therapies. Here, we explored the possibility of antibody therapy or vaccination against intracellular proteins. As proofs of concept, we selected three representative intracellular proteins as immunogens for tumor vaccine studies: PRL-3 (phosphatase of regenerating liver 3), a cancer-associated phosphatase; EGFP (enhanced green fluorescent protein), a general reporter; and mT (polyomavirus middle T), the polyomavirus middle T oncoprotein. A variety of tumors that expressed these intracellular proteins were clearly inhibited by their respective exogenous antibodies or by antigen-induced host antibodies (vaccination). These anticancer activities were reproducibly observed in hundreds of C57BL/6 tumor-bearing mice and MMTV-PymT transgenic breast tumor mice. Our in vivo data suggest that immunotherapies can target not only extracellular but also intracellular oncoproteins.
authors: Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Proteos, Republic of Singapore.
authors: Ke
authors: K
authors: Guo
authors: Jie
authors: J
authors: Li
authors: Jing Ping
authors: JP
authors: Tang
authors: Cheng Peow Bobby
authors: CP
authors: Tan
authors: Cheng William
authors: CW
authors: Hong
authors: Abdul Qader O
authors: AQ
authors: Al-Aidaroos
authors: Leyon
authors: L
authors: Varghese
authors: Caixia
authors: C
authors: Huang
authors: Qi
authors: Q
authors: Zeng
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D049452:Green Fluorescent Proteins / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D015513:Oncogene Proteins / Q000276:immunology*; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D015996:Survival Rate; D014611:Vaccination
chemical_list: D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D017874:Immediate-Early Proteins; D015513:Oncogene Proteins; C111534:Ptp4a3 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017027:Protein Tyrosine Phosphatases