The protective effect of CD40 ligand–CD40 signalling is limited during the early phase of Plasmodium infection

Abstractγδ T cells are essential for eliminating Plasmodium berghei XAT. Because administration of the agonistic anti-CD40 antibody can induce elimination of P. berghei XAT parasites in γδ T cell-deficient mice, we considered that γδ T cells might activate dendritic cells via CD40 signalling during infection. Here we report that administration of the anti-CD40 antibody to γδ T cell-deficient mice 3–10days post-P. berghei XAT infection could eliminate the parasites. Our data suggest that dendritic cell activation via γδ T cells expressing CD40 ligand is critical during the early phase of infection

Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies

Abstract Background Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2. Methods ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines. Results EGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50—80% cytotoxicity against four primary glioblastoma lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133– and CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets. Conclusion High-grade gliomas are suitable for specific targeting by armed ATC. These data, together with additional animal studies, may provide the preclinical support for the use of armed ATC as a valuable addition to current treatment regimens

Estimation of Proton Mobility in HZSM-5 Type Zeolite Films by Complex Impedance Method <Note>

The delocalization of protons in HZSM-5 type zeolite films was investigated by the complex impedance method. The conductivities under various water vapor pressures were calculated from both the Cole-Cole plot analysis and the impedance at 1 kHz. The conductivity of HZSM-5 (Al) zeolite film with 170 of SiO2/Al2O3 ratio was strongly dependent on the water vapor pressure and increased with an increase inthe vapor pressure. On the other hand, the conductivities of the silicalite film (SiO2/Al2O3 ratio > 5000) and the pellet prepared by compressing the powdery HZSM-5 zeolite with 173 of SiO2/Al2O3 ratio hardly increased with the water vapor pressure. The conductivities of HZSM-5 type metallosilicates (HZSM-5 (Ga) and HZSM-5 (Fe)) films were also measured. From the results obtained, it was concluded that (1) the acidic sites associated with the framework aluminums are the active centers for the proton conductivity, (2) adsorbed water molecules are responsible for the conduction and (3) the polycrystalline zeolite film is very effective for estimation of proton mobility