Anti-CD4 monoclonal antibody, clone wqh49

The present study was designed to evaluate percentage of lymphocyte subsets in peripheral blood mononuclear cells of pulmonary tuberculosis patients with diabetes mellitus (TBDM) and household contacts (HHC) at the time of diagnosis and at different intervals of follow-up. T-lymphocyte subsets, monocytes and natural killer cells were evaluated using fluorescence associated cell sorting (FACS) in a total of 125 subjects including TBDM, pulmonary tuberculosis (PTB) patients, HHC, diabetes mellitus (DM) patients and healthy controls (HC), 25 in each category. CD4 proportion was significantly low in TBDM (p = 0.003), PTB (p = 0.0008) and HHC (p = 0.005) when compared to HCs and increased with treatment in PTB at 6 M and 12 M (p = 0.008). CD8 percentage was significantly low in DM (p = 0.01); Significantly high mean percentage was observed with respect to CD14 in TBDM (p = 0.008), PTB (p = 0.018), HHC (p = 0.008) and DM (p = 0.014); with CD16 in TBDM (p = 0.0001), PTB (p = 0.0001), HHC (p = 0.045); with CD56 in TBDM (p = 0.0003), PTB (p = 0.002) and HHC (p = 0.015) respectively when compared to HCs. These results indicate that TBDM patients have altered lymphocyte homeostasis and FACS analysis might have the potential of a non-invasive clinical indicator for the early detection and monitoring of TB in HHC.

Rationale: The low response rate of immunotherapy, such as anti-PD-L1/PD-1 and anti-CTLA4, has limited its application to a wider population of cancer patients. One widely accepted view is that inflammation within the tumor microenvironment is low or ineffective for inducing the sufficient infiltration and/or activation of lymphocytes. Here, a highly tumor-selective anti-PD-L1 (alpha PD-L1) antibody was developed through PET imaging screening, and it was radiolabeled with Lu-177 for PD-L I -targeted radioimmunotherapy (RIT) and radiation-synergized immunotherapy. Methods: A series of alpha PD-L1 antibodies were radiolabeled with zirconium-89 for PET imaging to screen the most suitable antibodies for RIT. Mice were divided into an immunotherapy group, a RIT group and a radiation-synergized immunotherapy group to evaluate the therapeutic effect. Alterations in the tumor microenvironment after treatment were assessed using flow cytometry and immunofluorescence microscopy. Results: Radiation-synergistic RIT can achieve a significantly better therapeutic effect than immunotherapy or RIT alone. The dosages of the radiopharmaceuticals and alpha PD-L1 antibodies were reduced, the infiltration of CD4(+) and CD8(+) T cells in the tumor microenvironment was increased, and no side effects were observed. This radiation-synergistic RIT strategy successfully showed a strong synergistic effect with alpha PD-L1 checkpoint blockade therapy, at least in the mouse model. Conclusions: PET imaging of Zr-89-labeled antibodies is an effective method for antibody screening. RIT with a Lu-177-labeled alpha PD-L1 antibody could successfully upregulate antitumor immunity in the tumor microenvironment and turn "cold" tumors "hot" for immunotherapy.