In vitro and in vivo Evidence on Intra-tumor Injection of Allogeneic Serum for Immunotherapy in a Mouse Model of Colon Cancer.

It is believed that preformed antibodies are responsible for blood transfusion reactions and transplant rejections. In order to remove a tumor, the tissue must be rejected. On the basis of transfusion reaction and transplantation immunology, we hypothesized that allogeneic serum can inhibit tumor growth when injected intra-tumor. Initially, an in vitro cytotoxicity test was conducted using the C57BL/6 serum (intact or decomplemented) in combination with the BALB/c-originating CT26 cell line.  The CT26 cell line was used to establish a mouse model of colon cancer. When the tumor was palpable, C57BL/6 serum was injected intra-tumor. In addition to tumor size, hypoxia, metastatic capacity, angiogenesis, and metabolic and inflammatory status, we evaluated matrix metalloproteinase-2 (MMP)-2 and 9, vascular endothelial growth factor (VEGF)-A, Cluster of Designation (CD) 31, CD38 and interleukine (IL)-10. An in vitro experiment showed that heat-inactivated C57BL/6 serum had significantly lower cytotoxic effects on BALB/c-derived CT26 cells than intact C57BL/6 serum or BALB/c serum. In vivo experiments revealed that tumor size, HIF-1α, MMP-2, and MMP-9 levels were significantly lower in the experimental group than in the control group. In contrast to control animals, allogeneic serum treatment led to marked reductions in CD31, VEGF-1, CD38, and IL-10 levels. A new approach to serum or plasma therapy and allogeneic vaccines for cancer is intra-tumor injection of allogeneic serum. In light of the ease and availability of allogeneic immunotherapies, allogeneic serum and plasma therapy could potentially be used as an alternative monotherapy or in combination with other therapies.

Harmony of T cell profile in brain, nasal, spleen, and cervical lymph nodes tissues in Alzheimer's: A systemic disease with local manifestations.

The brain has special importance and is known as immune privileged site to and from which trafficking of immune cells is tightly regulated. However, in Alzheimer's disease (AD) the balance of the immune system is disturbed and damages the brain. Given the anatomical and immunological barriers in the brain, we attempted to evaluate if the neuroinflammation occurred in AD is limited to the brain or is expanded to the periphery. Hence, rat model of AD was induced by intra-hippocampal injection of beta-amyloid1-42. Then, nasal, brain, cervical lymph nodes, and spleen were isolated. Then, profile of T-helper (Th)1, Th2, and Th17, represented by IFN-γ, IL-4, and IL-17, respectively, was determined. The results were compared between the organs and with the corresponding tissue in normal animals. IFN-γ and IL-17 levels in the brain, nasal tissue, and cervical lymph nodes of AD model were higher than IL-4, comparing with normal animals. Similar profile was observed in the spleen. The results suggest Alzheimer's as a systemic disease whose complication are observed locally. The possibility of epitope spreading and autoimmune nature of AD is raised again. Interestingly, although AD model was induced by injection of beta-amyloid in the brain, the cellular responses in the brain and nasal tissue were similar indicating that the nasal-brain axis is two-sided. In addition, both of IFN-γ/IL-17 and IL-4/IL-17 ratios, just in nasal tissue were markedly decreased in AD model comparing with normal animals. This suggests development of future nasal-based diagnostic approaches.