A phase II open label, randomized clinical trial of atezolizumab with or without human recombinant IL-7 (CYT107) in advanced urothelial cancer.

Purpose: Advanced urothelial cancer generally has high mortality despite modern anti-PD-1/L1 antibody-based combinations. Augmenting checkpoint inhibitor-mediated immune responses with lymphocyte growth factors may improve outcomes. We conducted a randomized phase II study (CITN-14) in 47 patients to explore whether human recombinant IL-7 (CYT107) could be safely combined with PD-L1 inhibition to enhance responses.

Peripheral blood CD4 T-cell and plasmacytoid dendritic cell (pDC) reactivity to herpes simplex virus 2 and pDC number do not correlate with the clinical or virologic severity of recurrent genital herpes.

Leukocytes participate in the immune control of herpes simplex virus (HSV). Data from HIV coinfections, germ line mutations, and case reports suggest involvement of CD4 T cells and plasmacytoid dendritic cells (pDC). We investigated the relationships between these cells and recurrent genital herpes disease severity in the general population.

DNA vaccine delivery by densely-packed and short microprojection arrays to skin protects against vaginal HSV-2 challenge.

There is an unmet medical need for a prophylactic vaccine against herpes simplex virus (HSV). DNA vaccines and cutaneous vaccination have been tried for many applications, but few reports combine this vaccine composition and administration route. We compared DNA administration using the Nanopatch™, a solid microprojection device coated with vaccine comprised of thousands of short (110 μm) densly-packed projections (70 μm spacing), to standard intramuscular DNA vaccination in a mouse model of vaginal HSV-2 infection.

Improved DNA vaccination by skin-targeted delivery using dry-coated densely-packed microprojection arrays.

HSV-2-gD2 DNA vaccine was precisely delivered to immunologically sensitive regions of the skin epithelia using dry-coated microprojection arrays. These arrays delivered a vaccine payload to the epidermis and the upper dermis of mouse skin. Immunomicroscopy results showed that, in 43 ± 5% of microprojection delivery sites, the DNA vaccine was delivered to contact with professional antigen presenting cells in the epidermal layer.

Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivo.

CD1d-restricted NKT cells rapidly stimulate innate and adaptive immunity through production of Th1 and/or Th2 cytokines and induction of CD1d(+) APC maturation. However, therapeutic exploitation of NKT cells has been hampered by their paucity and defects in human disease. NKT cell-APC interactions can be modeled by direct stimulation of human APCs through CD1d in vitro.