Cost-effectiveness analysis of 10- and 13-valent pneumococcal conjugate vaccines in Peru

This study was made possible through the financial support of the Instituto Nacional de Salud (National Institute of Health, Lima, Peru) and the PROVAC Initiative of the Pan American Health Organization (Washington, DC, USA). This study was presented at 9th International Symposium of Pneumococci and Pneumococcal Diseases, Hyderabad, India, March 2014, and supported by the National Council of Science, Technology and Technological Innovation of Peru (CONCYTEC) and International Clinical Epidemiology Network (INCLEN Trust).Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica - Concyte

CD137 (4-1BB) costimulation of CD8+ T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation

CD137 (4-1BB; TNFSR9) is an activation-induced surface receptor that through costimulation effects provide antigen-primed T cells with augmented survival, proliferation and effector functions as well as metabolic advantages. These immunobiological mechanisms are being utilised for cancer immunotherapy with agonist CD137-binding and crosslinking-inducing agents that elicit CD137 intracellular signaling. In this study, side-by-side comparisons show that provision of CD137 costimulation in-cis with regard to the TCR-CD3-ligating cell is superior to that provided in-trans in terms of T cell activation, proliferation, survival, cytokine secretion and mitochondrial fitness in mouse and human. Cis ligation of CD137 relative to the TCR-CD3 complex results in more intense canonical and non-canonical NF-κB signaling and provides a more robust induction of cell cycle and DNA damage repair gene expression programs. Here we report that the superiority of cis versus trans CD137-costimulation is readily observed in vivo and is relevant for understanding the immunotherapeutic effects of CAR T cells and CD137 agonistic therapies currently undergoing clinical trials, which may provide costimulation either in cis or in trans