Pancreatic ductal adenocarcinoma(PDAC) has the poorest prognosis of all malignancies and is largely resistant to standard therapy. Novel treatments against PDAC are desperately needed. Anti-Gal is the most abundant na...Pancreatic ductal adenocarcinoma(PDAC) has the poorest prognosis of all malignancies and is largely resistant to standard therapy. Novel treatments against PDAC are desperately needed. Anti-Gal is the most abundant natural antibody in humans,comprising about 1% of immunoglobulins and is also naturally produced in apes and Old World monkeys. The anti-Gal ligand is a carbohydrate antigen called "α-gal epitopes" with the structure Galα1-3Galβ1-4Glc NAc-R. These epitopes are expressed as major carbohydrate antigens in non-primate mammals,prosimians,and New World monkeys. Anti-Gal is exploited in cancer vaccines to increase the immunogenicity of antigen-presenting cells(APCs). Cancer cells or PDAC tumor lysates are processed to express α-gal epitopes. Vaccination with these components results in in vivo opsonization by anti-Gal Ig G in PDAC patients. The Fc portion of the vaccine-bound anti-Gal interacts with Fcγ receptors of APCs,inducing uptake of the vaccine components,transport of the vaccine tumor membranes to draining lymph nodes,and processing and presentation of tumor-associated antigens(TAAs). Cancer vaccines expressing α-gal epitopes elicit strong antibody production against multiple TAAs contained in PDAC cells and induce activation of multiple tumor-specific T cells. Here,we review new areas of clinical importance related to the α-gal epitope/anti-Gal antibody reaction and the advantages in immunotherapy against PDAC.展开更多
AIM: To investigate into the diversity of UGT1A1 polymorphism across three different districts in Japan and highlight genetic differences among the population in Japan. METHODS: We enrolled 50 healthy volunteers from ...AIM: To investigate into the diversity of UGT1A1 polymorphism across three different districts in Japan and highlight genetic differences among the population in Japan. METHODS: We enrolled 50 healthy volunteers from each of the Yamaguchi (western part of Japan), Kochi(southern part of Japan) and Akita (northern part of Japan) prefectures. Blood samples (7 mL) were collected from each participant and stored in EDTA for subsequent genotyping by fragment size analysis, direct sequencing and TaqMan assay of UGT1A1*28, UGT1A7*3/UGT1A9*22 and UGT1A1*93/UGT1A1*6/ UGT1A1*27/UGT1A1*60/UGT1A7 (-57), respectively. RESULTS: The only statistically significant differences in allele polymorphisms among the group examined were for UGT1A1*6. The Akita population showed more UGT1A1*6 heterozygosity (P = 0.0496). CONCLUSION: Our study revealed no regional diversity among UGT1A1, UGT1A7 or UGT1A9 polymorphisms in Japan.展开更多
基金Supported by Ministry of Education,Sports and Culture of Japan to M.T.,No.25462129
文摘Pancreatic ductal adenocarcinoma(PDAC) has the poorest prognosis of all malignancies and is largely resistant to standard therapy. Novel treatments against PDAC are desperately needed. Anti-Gal is the most abundant natural antibody in humans,comprising about 1% of immunoglobulins and is also naturally produced in apes and Old World monkeys. The anti-Gal ligand is a carbohydrate antigen called "α-gal epitopes" with the structure Galα1-3Galβ1-4Glc NAc-R. These epitopes are expressed as major carbohydrate antigens in non-primate mammals,prosimians,and New World monkeys. Anti-Gal is exploited in cancer vaccines to increase the immunogenicity of antigen-presenting cells(APCs). Cancer cells or PDAC tumor lysates are processed to express α-gal epitopes. Vaccination with these components results in in vivo opsonization by anti-Gal Ig G in PDAC patients. The Fc portion of the vaccine-bound anti-Gal interacts with Fcγ receptors of APCs,inducing uptake of the vaccine components,transport of the vaccine tumor membranes to draining lymph nodes,and processing and presentation of tumor-associated antigens(TAAs). Cancer vaccines expressing α-gal epitopes elicit strong antibody production against multiple TAAs contained in PDAC cells and induce activation of multiple tumor-specific T cells. Here,we review new areas of clinical importance related to the α-gal epitope/anti-Gal antibody reaction and the advantages in immunotherapy against PDAC.
基金Supported by The Non-profit Epidemiological and Clinical Research Information Network Organization
文摘AIM: To investigate into the diversity of UGT1A1 polymorphism across three different districts in Japan and highlight genetic differences among the population in Japan. METHODS: We enrolled 50 healthy volunteers from each of the Yamaguchi (western part of Japan), Kochi(southern part of Japan) and Akita (northern part of Japan) prefectures. Blood samples (7 mL) were collected from each participant and stored in EDTA for subsequent genotyping by fragment size analysis, direct sequencing and TaqMan assay of UGT1A1*28, UGT1A7*3/UGT1A9*22 and UGT1A1*93/UGT1A1*6/ UGT1A1*27/UGT1A1*60/UGT1A7 (-57), respectively. RESULTS: The only statistically significant differences in allele polymorphisms among the group examined were for UGT1A1*6. The Akita population showed more UGT1A1*6 heterozygosity (P = 0.0496). CONCLUSION: Our study revealed no regional diversity among UGT1A1, UGT1A7 or UGT1A9 polymorphisms in Japan.
