Search

Aim: The Thomsen-Friedenreich antigen (TF-Ag) is a disaccharide hidden on normal cells, but selectively exposed on the surface of breast, colon, prostate and bladder cancer cells. JAA-F11, a highly specific monoclonal antibody to TF-Ag, reduces metastasis and prolongs survival in a mouse model. In addition,(124)I-JAA-F11 localizes 4T1 tumors in mice. These studies continue translation of JAA-F11 to human breast cancer. MATERIALS & METHODS & RESULTS: Of the 41 human breast cancer cell lines tested, 78% were positive for reactivity with JAA-F11 by whole-cell enzyme immunoassay and positivity occurred unrelated to estrogen, progesterone or HER2 receptor status. JAA-F11 inhibited the growth rate of the human cancer cell lines tested. At 1 h, approximately 80% of JAA-F11 internalized in the three cell lines tested. (124)I-JAA-F11 specifically imaged human triple-negative tumors in mice by microPET.Conclusion: The results highlight the potential that humanized JAA-F11 may have for immunotherapy and drug conjugate therapy in breast cancer patients. [ABSTRACT FROM AUTHOR]

An in-house loop-mediated isothermal amplification ( LAMP) method was established for the detection of S almonella Typhi and S almonella Paratyphi A using primers that were designed based on gene coding for putative regulatory protein in S. Typhi ( STY4220) and S. Paratyphi A ( SSPA3213). This established in-house LAMP assay gave positive results to all the 14 S. Typhi and 20 S. Paratyphi A isolates used in this study and negative to 20 other S almonella and 19 non- S almonella bacteria. When tested on 60 clinical samples, it gave positive results to 10 clinical samples containing either S. Typhi or S. Paratyphi A and negative to the other 50 samples, which were similar to those results obtained by gold standard culture method. Because of its rapidity and simplicity, this LAMP offers a promising method for the detection of both S. Typhi and S. Paratyphi A for screening purposes at resource-limited settings. Practical Applications Current detection methods for S. Typhi and S. Paratyphi A have several limitations; culture method is time-consuming and laborious, while polymerase chain reaction-based methods require expensive equipments and trained personnel which are usually not available in the low-resource setting. Therefore, LAMP established in this study offers a simple, rapid, sensitive and specific method for the screening of S. Typhi and S. Paratyphi A especially at resource-limited settings. [ABSTRACT FROM AUTHOR]

Thomsen-Friedenreich antigen (TF-Ag) is the disaccharide (Gal beta1-3 GalNAc alpha), which is also known as the core 1 structure. The presence of this disaccharide on the surface of approximately 90 percent of carcinomas is due to altered glycosylation in these tumors. TF-Ag plays a role in the adhesive properties of tumor cells involved in metastasis. Treatment of mice with JAA-F11, a monoclonal antibody to TF-Ag alpha inhibited lung metastasis and improved prognosis in a mouse breast cancer model. The presence of naturally occurring antibodies to TF-Ag in cancer patients is related to improved prognosis. The pancarcinoma expression of TF-Ag, combined with the evidence of a mechanistic role for TF-Ag in cancer spread, show that this target would have clinical utility. The presence of naturally occurring antibody to TF-Ag indicates that increasing the anti-TF-Ag antibody would be safe for the cancer patient and indicates that tolerance would not have to be broken to create this immune response. Finally, the prognostic improvements seen clinically and in animal models indicate that this is an important vaccine target.