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Designer Glycopeptides for Cytotoxic T Cell-based Immunotherapy of Carcinomas

详细技术说明

UCSD researchers have demonstrated that human carbohydrate-specific cytotoxic T cells can be generated by immunizing in vitro. In addition, they have tested and shown that the glycopeptides can break immunological tolerance in wild type mice with well-established tumors that express the carbohydrate antigen. Characterization of Tn-specific CTL clones. Dose–response relationship of five representative anti-Tn CTL clones to AIIA(GalNAc-O-S)FAAL measured in a classical 51Cr release assay at a 2:1 E : T ratio. In vitro killing of the syngeneic mammary tumor cell line MMT and themelanoma cells transfected with MUC1 and B16/MUC1, by anti-Tn specific CTL clones measured at a 20:1 E : T ratio. (), 1A7;(   ), 3B9; (), 1B3; (), 4E5; (), 1C8.From Ref (2) below.

*Abstract

Tumor Associated Carbohydrate Antigens (TACA) (or carbohydrate-peptide conjugates) are utilized to generate cytotoxic T lymphocytes for a pan-cancer immune response.

Thomsen-Friedenreich antigen (TF) and its monomer (Tn) are glycoproteins that bind with high affinity to the major histocompatibility complex (MHC). TF and Tn are also tumor associated TACAs that are usually present on cancer cell surfaces in a cryptic form covered by N-acetyl neuraminic acid moieties and released into circulation in many different cancers. The fact that TACAs are not expressed in normal tissues presents a unique target for immunotherapy, if TACA can be designed to be more accessible and recognizable by the immune system.

While both tumor-derived peptides and tumor-derived carbohydrate antigens have been used in anti-cancer therapy, using a glycopeptide can potentially increase the efficacy of the immunotherapy.

*IP Issue Date

Oct 13, 2015

*Principal Investigation

Name: Alessandra Franco

Department:

附加资料

Patent Number: US20110045046A1
Application Number: US2010918155A
Inventor: Franco, Alessandra
Priority Date: 26 Feb 2008
Priority Number: US20110045046A1
Application Date: 10 Nov 2010
Publication Date: 24 Feb 2011
IPC Current: A61K0009127 | A61K000900 | A61K000914 | A61K003814 | A61K003900 | A61P003500 | A61P003704 | C07K000900 | C12N00050783
US Class: 424422 | 4241851 | 424450 | 435325 | 5140193 | 5140214 | 5140215 | 5140216 | 5140217 | 530322
Assignee Applicant: The Regents of the University of California
Title: GLYCOPEPTIDES AND METHODS OF MAKING AND USING THEM
Usefulness: GLYCOPEPTIDES AND METHODS OF MAKING AND USING THEM
Summary: (I) is useful in a composition, which is formulated as a vaccine for treating, preventing or ameliorating a disease or condition associated with a dysfunctional cell or a cancer or a tumor cell, for treating, preventing or ameliorating cancer or a tumor, or to prevent, decrease the amount of or ameliorate metastasis a cancer or a tumor, where the cancer is e.g. epithelial origin, a lymphoma, Hodgkin's disease, a chronic or acute leukemia, a lymphocytic lymphoma leukemia, a neoplasm of CNS, a primary CNS lymphoma, a spinal axis tumor, a brain stem glioma, a pituitary adenoma or a cutaneous or systemic melanoma. (I) is useful: to generate (elicit) an antigen-specific cytotoxic lymphocyte response and/or an antigen-specific helper T cell response, and/or a cluster of differentiation (CD)8+ or a CD4+ T cell response; and for lowering prostate serum antigen serum levels in an individual and for inducing (eliciting) an anti-tumor antigen antibody humoral B cell response (all claimed).
Novelty: New isolated glycopeptide (glycoconjugate) comprising e.g. at least one carbohydrate moiety conjugated (linked) to tumor-associated antigen-derived peptide, is vaccine useful to treat e.g. carcinoma, lymphoma and Hodgkin's disease

主要类别

诊断/治疗

细分类别

癌症/肿瘤

申请号码

9156906

其他

Related Materials

Glycoconjugates as vaccines for cancer immunotherapy: clinical trials and future directions; Franco A. Anticancer Agents Med Chem 2008 Jan; 8(1) 86-91 Review. PMID 18220508
Tumor associated carbohydrate antigens: a possible avenue for cancer prevention. Franco et al; Immunol Cell Biol., 2005 Aug; 83(4) 440-8 PMID 16033540
CTL-based cancer preventive/therapeutic vaccines for carcinomas; role of tumor associated carbohydrate antigens. Franco A.; Scand J Immunol. 2005 May; 61 (5): 391-7 Review. PMID 15882430
Designer glycopeptides for cytotoxic T cell-based elimination of carcinomas. Franco et al. J Exp Med. 2004 Mar 1; 199(5); 707-16 PMID 14993254
Designer glycopeptides for cytotoxic T cell-based elimination of carcinomas. Franco et al. J Exp Med. 2004 Mar 1; 199(5); 707-16 PMID 14993254

Tech ID/UC Case

23024/2008-189-0

Related Cases

2008-189-0

国家/地区

美国