Enhanced Immune Recognition of Cryptic Glycan Markers in Human Tumors (original) (raw)
Related papers
Cancer Gene Therapy, 2003
The interaction between Fas and Fas ligand (FasL) is involved in the apoptotic death of a number of cells including lymphocytes. Forced expression of FasL in tumors can induce apoptosis of infiltrating Fas-positive T cells; accordingly, tumors can survive in the milieu of systemic immune responses. However, FasL-expressing murine lung carcinoma (A11) and melanoma (B16) cells did not develop subcutaneous tumors and FasL-expressing A11 (A11 / FasL) cells produced few spontaneous lung metastatic foci in syngeneic mice. The mice that rejected A11 / FasL cells were resistant to subsequent challenge of parent A11 but not irrelevant B16 cells. Vaccination of mice with UV-treated A11 / FasL, but not UV-treated A11 cells, however, augmented the growth rate of A11 but not B16 tumors, both of which were subsequently inoculated. The number of lung metastatic foci of A11 cells was also increased in the mice that received UV-treated A11 / FasL but not UV-treated A11 cells. Intraperitoneal injection of UV-treated A11 / FasL cells resulted in the production of larger amounts of immunosuppressive TGFb in peritoneal exudate than that of UV-treated A11 cells. Expression of the CD80 costimulatory molecule in tissues where UV-treated A11 / FasL cells were inoculated was lower than the expression at an untreated A11 / FasL-injected site. Our results indicated that apoptotic FasL-expressing tumor cells could impair host immune responses against the tumors, in contrast to potent antitumor immunity generated by viable FasL-expressing tumors.
Mucosally restricted antigens as novel immunological targets for antitumor therapy
Biomarkers in Medicine, 2007
Colorectal cancer is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. While surgery remains the mainstay of therapy, approximately 50% of persons who undergo resection develop parenchymal metastatic disease. Unfortunately, current therapeutic regimens offer little improvement in survival. Using immunotherapy to fill this therapeutic gap has enjoyed limited success, reflecting a paucity of tumor-associated antigens. In that context, there is a significant unrealized opportunity to exploit structural and functional immune system compartmentalization to generate a therapeutic immune response against metastatic colorectal tumors employing biomarkers whose expression is normally confined to intestinal epithelial cells and their derivative malignancies. This novel class of biomarkers, here termed cancer mucosa antigens, may fill the unmet therapeutic need for colorectal cancer-associated immune targets. As a concrete example, guanylyl cyclase C is an intestinal mucosa-specific biomarker ideally suited to test this hypothesis and serve as the first cancer mucosa antigen for colorectal cancer immunotherapy. Here, we discuss colorectal cancer immunity, immune compartmentalization and preliminary results targeting guanylyl cyclase C in mouse models of colorectal cancer, as well as the potential paradigm shift to employing cancer mucosa antigens in immunotherapy of colorectal cancer.
Fas ligand breaks tolerance to self-antigens and induces tumor immunity mediated by antibodies
Cancer Cell, 2002
FasL, rejection often occurs as a consequence of proinflammatory functions of FasL. Here we demonstrate that FasL elicits tumor immunity in a murine melanoma model with weak immunogenicity and low expression of major histocompatibility complex (MHC) class I. We show that protected mice recognize melanocyte differentiation self-antigens. Importantly, tumor immunity is mediated by antibodies, as it can be transferred by serum from protected mice.
Cellular and humoral immune responses against cancer: implications for cancer vaccines
Current Opinion in Immunology, 1991
The key issue in tumor immunology is to identify antigens as target structures for a cancer-selective immunological attack in the tumor-bearing host, resulting in tumor rejection. There is a growing detailed understanding of structural and regulatory gene alterations giving rise to candidate rejection antigens and peptides in tumor cells. As well as reviewing the development of new adjuvant and recombinant vector systems, new approaches are suggested for the construction of cancer vaccines. Current Opinion in Immunology 1991, 3:659664 Abbreviations BCG-bacillus Calmette-Guerin; Cll-ytolytic T lymphocyte; C-CSF-granulocyte colony-stimulating factor; IFN-interferon; IL-interleukin; MHC-major histocompatibility complex; MLTC-mixed lymphocyte tumor cell culture; TNF-tumor necrosis factor; UV-ultraviolet. @ Current Biology Ltd ISSN 0952-7915 659 of outstanding interest PREHN RT, ~+AIN JM Immunity to Methylcholanthreneinduced Sarcomas.
Cancer vaccines and carbohydrate epitopes
Vaccine, 2011
Tumor-associated carbohydrate antigens (TACA) result from the aberrant glycosylation that is seen with transformation to a tumor cell. The carbohydrate antigens that have been found to be tumor-associated include the mucin related Tn, Sialyl Tn, and Thomsen-Friedenreich antigens, the blood group Lewis related Lewis Y , Sialyl Lewis X and Sialyl Lewis A , and Lewis X , (also known as stage-specific embryonic antigen-1, SSEA-1), the glycosphingolipids Globo H and stage-specific embryonic antigen-3 (SSEA-3), the sialic acid containing glycosphingolipids, the gangliosides GD2, GD3, GM2, fucosyl GM1, and Neu5GcGM3, and polysialic acid. Recent developments have furthered our understanding of the T-independent type II response that is seen in response to carbohydrate antigens. The selection of a vaccine target antigen is based on not only the presence of the antigen in a variety of tumor tissues but also on the role this antigen plays in tumor growth and metastasis. These roles for TACAs are being elucidated. Newly acquired knowledge in understanding the T-independent immune response and in understanding the key roles that carbohydrates play in metastasis are being applied in attempts to develop an effective vaccine response to TACAs. The role of each of the above mentioned carbohydrate antigens in cancer growth and metastasis and vaccine attempts using these antigens will be described.