Nanotechnology Promotes Genetic and Functional Modifications of Therapeutic T Cells Against Cancer.

Growing experience with engineered chimeric antigen receptor (CAR)-T cells has revealed some of the challenges associated with developing patient-specific therapy. The promising clinical results obtained with CAR-T therapy nevertheless demonstrate the urgency of advancements to promote and expand its uses. There is indeed a need to devise novel methods to generate potent CARs, and to confer them and track their anti-tumor efficacy in CAR-T therapy. A potentially effective approach to improve the efficacy of CAR-T cell therapy would be to exploit the benefits of nanotechnology. This report highlights the current limitations of CAR-T immunotherapy and pinpoints potential opportunities and tremendous advantages of using nanotechnology to 1) introduce CAR transgene cassettes into primary T cells, 2) stimulate T cell expansion and persistence, 3) improve T cell trafficking, 4) stimulate the intrinsic T cell activity, 5) reprogram the immunosuppressive cellular and vascular microenvironments, and 6) monitor the therapeutic efficacy of CAR-T cell therapy. Therefore, genetic and functional modifications promoted by nanotechnology enable the generation of robust CAR-T cell therapy and offer precision treatments against cancer.

Vaccination with Consensus H7 Elicits Broadly Reactive and Protective Antibodies against Eurasian and North American Lineage H7 Viruses.

H7 subtype avian influenza viruses have caused outbreaks in poultry, and even human infection, for decades in both Eurasia and North America. Although effective vaccines offer the best protection against avian influenza viruses, antigenically distinct Eurasian and North American lineage subtype H7 viruses require the development of cross-protective vaccine candidates. In this study, a methodology called computationally optimized broadly reactive antigen (COBRA) was used to develop four consensus H7 antigens (CH7-22, CH7-24, CH7-26, and CH7-28). In vitro experiments confirmed the binding of monoclonal antibodies to the head and stem domains of cell surface-expressed consensus HAs, indicating display of their antigenicity. Immunization with DNA vaccines encoding the four antigens was evaluated in a mouse model. Broadly reactive antibodies against H7 viruses from Eurasian and North American lineages were elicited and detected by binding, inhibition, and neutralizing analyses. Further infection with Eurasian H7N9 and North American H7N3 virus strains confirmed that CH7-22 and CH7-24 conferred the most effective protection against hetero-lethal challenge. Our data showed that the consensus H7 vaccines elicit a broadly reactive, protective response against Eurasian and North American lineage H7 viruses, which are suitable for development against other zoonotic influenza viruses.