The antigenic similarity between embryos and tumors has raised the idea of using embryonic material as a preventative vaccine against neoplastic disease. Indeed, we have previously reported that a vaccine comprises allogeneic murine embryonic stem cells (ESCs) and murine fibroblasts expressing GM-CSF (to amplify immune responses) successfully blocks the outgrowth of an implantable cancer (Lewis lung carcinoma; LLC) and lung tumors generated in mice using a combination of a mutagen followed by chronic pulmonary inflammation. However, such a vaccine is obviously impractical for application to humans. The use of fibroblasts to generate GM-CSF is needlessly complicated, and intact whole ESCs carry the hazard of generating embryomas/teratomas. Here, we report the successful application of an alternative prophylactic vaccine comprises exosomes derived from murine ESCs engineered to produce GM-CSF. Vaccination of mice with these exosomes significantly slowed or blocked the outgrowth of implanted LLC while control exosomes lacking GM-CSF were ineffective. Examination of tumor-infiltrating immune cells from mice vaccinated with the GM-CSF-expressing exosomes showed robust tumor-reactive CD8 + T effector responses, Th1 cytokine responses, and higher CD8 + T effector/CD4 + CD25 + Foxp3 + T regulatory cell ratio in the tumors. We conclude that a similar vaccine derived from GM-CSF-expressing human ESCs can be employed as a preventative vaccine for humans with an increased risk of developing cancer.

Background Alcohol use is typically established during adolescence and initiation of use at a young age poses risks for short- and long-term health and social outcomes. However, there is limited understanding of the onset, progression and impact of alcohol use among adolescents in India. The aim of this review is to synthesise the evidence about prevalence, patterns and correlates of alcohol use and alcohol use disorders in adolescents from India. Methods Systematic review was conducted using relevant online databases, grey literature and unpublished data/outcomes from subject experts. Inclusion and exclusion criteria were developed and applied to screening rounds. Titles and abstracts were screened by two independent reviewers for eligibility, and then full texts were assessed for inclusion. Narrative synthesis of the eligible studies was conducted. Results Fifty-five peer-reviewed papers and one report were eligible for inclusion in this review. Prevalence of ever or lifetime alcohol consumption ranged from 3.9% to 69.8%; and prevalence of alcohol consumption at least once in the past year ranged from 10.6% to 32.9%. The mean age for initiation of drinking ranged from 14.4 to 18.3 years. Some correlates associated with alcohol consumption included being male, older age, academic difficulties, parental use of alcohol or tobacco, non-contact sexual abuse and perpetuation of violence. Conclusion The evidence base for alcohol use among adolescents in India needs a deeper exploration. Despite gaps in the evidence base, this synthesis provides a reasonable understanding of alcohol use among adolescents in India and can provide direction to policymakers.

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