Tumor-Associated Carbohydrate Antigen 19-9 (CA 19-9), a Promising Target for Antibody-Based Detection, Diagnosis, and Immunotherapy of Cancer.

Carbohydrate antigen 19-9 (CA 19-9) also known as sialyl Lewis A is a tetrasaccharide overexpressed on a wide range of cancerous cells, which has been detected at elevated levels in sera of patients with various types of malignancies, most prominently pancreatic ductal adenocarcinoma. After its identification in 1979, multiple studies have highlighted the significant roles of CA 19-9 in cancer progression, including facilitating extravasation and eventually metastases, proliferation of cancer cells, and suppression of the immune system. Therefore, CA 19-9 has been considered an attractive target for cancer diagnosis, prognosis, and therapy. This review discusses the synthesis of CA 19-9 antigen, elicitation of antibodies through vaccination, development of anti-CA 19-9 monoclonal antibodies, and their applications as imaging tracers and therapeutics for a variety of CA 19-9-positive cancer.

Stereoselective Synthesis of Sialyl Lewisa Antigen and the Effective Anticancer Activity of Its Bacteriophage Qß Conjugate as an Anticancer Vaccine.

Sialyl Lewisa (sLea ), also known as cancer antigen 19-9 (CA19-9), is a tumor-associated carbohydrate antigen. The overexpression of sLea on the surface of a variety of cancer cells makes it an attractive target for anticancer immunotherapy. However, sLea -based anticancer vaccines have been under-explored. To develop a new vaccine, efficient stereoselective synthesis of sLea with an amine-bearing linker was achieved, which was subsequently conjugated with a powerful carrier bacteriophage, Qß. Mouse immunization with the Qß-sLea conjugate generated strong and long-lasting anti-sLea IgG antibody responses, which were superior to those induced by the corresponding conjugate of sLea with the benchmark carrier keyhole limpet hemocyanin. Antibodies elicited by Qß-sLea were highly selective toward the sLea structure, could bind strongly with sLea -expressing cancer cells and human pancreatic cancer tissues, and kill tumor cells through complement-mediated cytotoxicity. Furthermore, vaccination with Qß-sLea significantly reduced tumor development in a metastatic cancer model in mice, demonstrating tumor protection for the first time by a sLea -based vaccine, thus highlighting the significant potential of sLea as a promising cancer antigen.

Single-Cell B-Cell Sequencing to Generate Natively Paired scFab Yeast Surface Display Libraries.

The immune cell profiling capabilities of single-cell RNA sequencing (scRNA-seq) are powerful tools that can be applied to the design of theranostic monoclonal antibodies (mAbs). Using scRNA-seq to determine natively paired B-cell receptor (BCR) sequences of immunized mice as a starting point for design, this method outlines a simplified workflow to express single-chain antibody fragments (scFabs) on the surface of yeast for high-throughput characterization and further refinement with directed evolution experiments. While not extensively detailed in this chapter, this method easily accommodates the implementation of a growing body of in silico tools that improve affinity and stability among a range of other developability criteria (e.g., solubility and immunogenicity).

A Systematic Review and Meta-Analysis on the Effect of Flavonoids on Insulin-like Growth Factor and Insulin-like Growth Factor Binding Protein and Incidence of Breast Cancer.

BACKGROUND: Insulin-like growth factor (IGF-1) is associated with breast cancer in menopausal women. Naturally occurring biomolecules found in common dietary protocols, such as flavonoids, play a key role in the inhibition and treatment of cancer. In-vitro/in-vivo studies showed that treatment involving flavonoids led to a reduced risk of breast cancer due to the decrease of IGF-1 level in addition to an increased insulin-like growth factor binding protein (IGFBP)-3. However, clinical studies did not show conclusive results in this regard because they are contradictory. OBJECTIVE: The aim of the present study was to find the effect of flavonoids on IGF-1 and IGFBP-3 and the incidence of breast cancer. METHODS: This systematic review was performed using PubMed, Scopus, ISI Web of Science, and EMBASE databases to collect results about the clinical use of flavonoids and their effects on breast cancer. After eliminating duplicate articles, the title and abstract of the remaining articles were examined in thematic communication, and related clinical articles were selected and studied based on inclusion criteria. The data were extracted from each article, and then statistical analysis was subsequently carried out by Comprehensive Meta-Analysis. RESULTS: The results showed that the effect of flavonoids on changes in IGF1 and IGFBP-3 was not statistically significant. No significant heterogeneity was detected across the studies. Pooled effect size also indicated that the mean change was not statistically significant. No significant heterogeneity was detected across the studies. There was no evidence of publication bias for IGF1 and IGFBP-3. CONCLUSION: This meta-analysis study suggests that flavonoid supplementations have no significant effect on IGF-1 and IGFBP-3, and a high soy diet has beneficial effects on IGF system components, which might be useful in breast cancer.