RESUMEN
Current cancer vaccines induce tumor-specific T cell responses without sustained tumor regression because immunosuppressive elements within the tumor induce exhaustion of effector T cells and infiltration of immune-suppressive regulatory T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs targeting members of the TNFR superfamily, such as OX40, 4-1BB, and GITR, expressed on effector T cells and Tregs, to reinvigorate T cell effector function and block Treg-suppressive function. In this article, we describe the development of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector CD4(+) and CD8(+) T cell proliferation, inhibit the induction of CD4(+) IL-10 -producing type 1 regulatory T cells, inhibit the expansion of ICOS(+)IL-10(+) Tregs, inhibit TGF-ß-induced FOXP3 expression on naive CD4(+) T cells, and block natural Treg-suppressive function. We humanized two anti-human OX40 mAb clones, and they retained the potency of their parental clones. These Abs should provide broad opportunities for potential combination therapy to treat a wide realm of cancers and preventative vaccines against infectious diseases.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Receptores OX40/antagonistas & inhibidores , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales Humanizados/metabolismo , Anticuerpos Monoclonales Humanizados/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Macaca mulatta , Ratones , Unión Proteica , Receptores OX40/metabolismoRESUMEN
Strain XA05 and FG03 with high biodegradation activity of phenol were isolated from the activated sludge and phenol-contaminated soils in Northwest of China, respectively. DNA sequencing and homologous analysis of 16s rRNA gene identified that XA05 belonged to an Acinetobacter sp. and FG03 was closely related to the Sphingomonas sp. Cells of strain XA05 and FG03 were mixed at the ratio of 1:1, and polyvinyl alcohol (PVA) was used as a gel matrix to immobilize mixed cells by repeated freezing and thawing. Biodegradation was evaluated by determining phenol. Detoxication was evaluated by using Daphnia magna toxicity tests. The removal effciency of phenol and factors affecting phenol degradation were investigated, the stability of the immobilized cells was also reported. Experimental values indicated that both free cells and immobilized cells showed high phenol degradation effciencies, higher than 95% within 35 h with an initial concentration of 800 mg/L phenol, and the immobilized cells showed better performance than that of the suspended-culture cells. These results indicate that immobilized Acinetobncter sp. XA05 and Sphingomonas sp. FG03 possesses a good application potential in the treatment of phenol-containing wastewater.