Anti-IL4 Monoclonal antibody, clone 9E5-9 [APC]

Targeting dendritic cells (DCs), either ex vivo (Ex. Sipuleucel-T) or in vivo, for stimulating cellular immunity has been a leading approach for cancer vaccines. We have rationally engineered a nanoparticle (NP)-based delivery system for vaccines (InAc-NPs) using inulin acetate (InAc) as the polymer to target DCs. The material and the antigen-encapsulated InAc-NPs (similar to 190 nm in diameter) were characterized for their physicochemical properties. As a potent vaccine adjuvant, InAc-NPs activated TLR4 on multiple immune cells, including DCs and primary swine and human cells, to secrete various cytokines as detected by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. In addition, InAc-NPs promoted the maturation of DCs as observed by a decreased phagocytic ability and enhanced capability to activate various maturation markers (MHC-I, MHC-II, CD40, and CD80) quantified using flow cytometry. In mice, the InAc-NPs produced strong serum antibody titers (total IgG, IgG1, and IgG2a) against the encapsulated antigen (ovalbumin) similar to complete Freund's adjuvant. Additionally, as a dose-sparing delivery system, antigen delivered through InAc-NPs generated higher antibody titers (IgG1, 1.57 times; IgG-total, 1.66 times; and IgG2a, 29.8 times) even at 100 times less antigen dose. High amounts of cytokines representing both humoral (IL4 and IL10) and cell-mediated (IL2 and IFN-gamma) immunities were secreted from splenocytes of mice immunized with InAc-NPs. Importantly, InAc-NPs provided complete protection in 100% of the vaccinated mice from metastasis of intravenously injected melanoma cells (B-16-F-10) to lungs. In addition, the InAc-NPs were cleared from the injection site within 30 h of injection (in vivo imaging) and displayed no toxicity at the injection site (histology). The current study demonstrates that the multifunctional InAc-based nanovaccine delivery system has potential applications in cancer immunotherapy and delivering vaccines against various infectious diseases.

Previous studies revealed that the intensity of spinal cord injury (SCI) plays a key role in the therapeutic effects induced by immunizing with neural-derived peptides (INDP), as severe injuries abolish the beneficial effects induced by INDP. In the present study, we analyzed the expression of some inflammation-related genes (IL6, IL12, IL-1 beta, IFNE pound, TNF alpha, IL-10, IL-4, and IGF-1) by quantitative PCR in rats subjected to SCI and INDP. We investigated the expression of these genes after a moderate or severe contusion. In addition, we evaluated the effect of INDP by utilizing two different peptides: A91 and Cop-1. After moderate injury, both A91 and Cop-1 elicited a pattern of genes characterized by a significant reduction of IL6, IL1 beta, and TNF alpha but an increase in IL10, IL4, and IGF-1 expression. There was no effect on IL-12 and INFE pound. In contrast, the opposite pattern was observed when rats were subjected to a severe spinal cord contusion. Immunization with either peptide caused a significant increase in the expression of IL-12, IL-1 beta, IFNE pound (pro-inflammatory genes), and IGF-1. There was no effect on IL-4 and IL-10 compared to controls. After a moderate SCI, INDP reduced pro-inflammatory gene expression and generated a microenvironment prone to neuroprotection. Nevertheless, severe injury elicits the expression of pro-inflammatory genes that could be aggravated by INDP. These findings correlate with our previous results demonstrating that severe injury inhibits the beneficial effects of protective autoimmunity.