Astragalus membranaceus-Derived Anti-Programmed Death-1 Monoclonal Antibodies with Immunomodulatory Therapeutic Effects against Tumors.

Astragalus membranaceus polysaccharide (APS) components are main ingredients of TCM and have proven efficacy to activate T cells and B cells, enhancing immunity in humans. In this study, elevated cytokine and anti-PD-1 antibody titers were found in mice after immunization with APS. Therefore, phage-display technology was utilized to isolate specific anti-programmed death-1 (PD-1) antibodies from mice stimulated by APS and to confirm whether the isolated anti-PD-1 antibody could inhibit the interaction of PD-1 with the programmed death-ligand 1 (PD-L1), resulting in tumor growth inhibition. The isolated single-chain fragment variable (scFv) S12 exhibited the highest binding affinity of 20 nM to PD-1, completed the interaction between PD-1 and PD-L1, and blocked the effect of PD-L1-induced T cell exhaustion in peripheral blood mononuclear cells in vitro. In the animal model, the tumor growth inhibition effect after scFv S12 treatment was approximately 48%. However, meaningful synergistic effects were not observed when scFv S12 was used as a cotreatment with ixabepilone. Moreover, this treatment caused a reduction in the number of tumor-associated macrophages in the tumor tissue. These experimental results indirectly indicate the ability of APS to induce specific antibodies associated with the immune checkpoint system and the potential benefits for improving immunity in humans.

Treatment With Biologic Agents Has Not Reduced Surgeries Among Patients With Crohn's Disease With Short Bowel Syndrome.

BACKGROUND & AIMS: Little is known about the effects of biologic agents used to treat Crohn's disease (CD) on its long-term complications, such as short bowel syndrome and intestinal failure (SBS-IF). We evaluated trends in small bowel resections and health care utilization among patients with CD with and without SBS-IF. METHODS: We collected data on the National Inpatient Sample on 2,989,185 patients hospitalized with CD in the United States before the time period in which CD was treated with biologic agents (1993-1997) and after biologic therapy became widespread (1998-2014). We used Poisson and linear regression analyses to evaluate trends for small bowel resections and health care utilization among patients with CD with and without SBS-IF. Multivariable models were adjusted for age, sex, Charlson-Deyo comorbidity index, payer source, hospital size, region, and teaching status. RESULTS: The proportions of patients who underwent resection did not significantly change during the period before biologic therapy (121.8 per 1000 hospitalizations in 1993 to 110.1 per 1000 hospitalizations in 1997; P trend =.14) but decreased significantly during the period after biologic therapy began (99.0 per 1000 hospitalizations in 1998 to 64.6 per 1000 hospitalizations in 2014; P trend < .01). However, among patients with SBS-IF, similar proportions of patients underwent resection during the period before biologic therapy (0.7 per 1000 hospitalizations in 1993 to 0.7 per 1000 hospitalizations in 1997; P trend = .92) and during the period after biologic therapy (0.6 per 1000 hospitalizations in 1998 to 0.7 per 1000 hospitalizations in 2014; P trend = .06). Rates of hospitalization for patients with SBS-IF increased from 16.5 per 1000 hospitalizations in 1998 to 19.5 per 1000 hospitalizations in 2014 (P trend < .01). SBS-IF hospitalizations were associated with longer lengths of stay (P < .01) and greater total charges (P < .01). CONCLUSIONS: In a study of the United States population, we found that the use of biologic agents to treat CD reduced the proportion of patients undergoing resection, but not among patients with SBS-IF. These findings indicate that biologic agents reduce some but not all features of CD. Studies are needed to identify patients at risk for SBS-IF, prevent and treat this complication, and identify new treatments.