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Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines. The clinical success of checkpoint blockade has underscored the role of peripheral tolerance mechanisms in limiting vaccine responses and highlighted the potential for combination therapies. Recent advances in transcriptome sequencing, computational modeling, and material engineering further suggest new opportunities to intensify cancer vaccines. This review will discuss the major approaches to therapeutic cancer vaccination and explore recent advances that inform the design of the next generation of cancer vaccines., (© 2016 Elsevier Inc. All rights reserved.)

Fopx3(+) expressing regulatory T cells (Tregs) function as an indispensable cellular constituent of the immune system by establishing and maintaining immunological self-tolerance. T cell receptor (TCR) ligands of high agonist activity, when applied in vivo under subimmunogenic conditions, convert naive but not activated T cells into stable Tregs expressing Foxp3. Tolerogenic vaccination with strong-agonist mimetopes of self-antigens may function as a safe and highly specific instrument in the prevention of autoimmune disease by promoting self-antigen-specific tolerance. In this review, we address the requirements for generation of dominant tolerance exerted by Foxp3(+) Tregs in autoimmune disease with special focus on type 1 diabetes (T1D). Further understanding of differentiation of T cells into Tregs at the cellular and molecular level will facilitate development of additional tolerogenic vaccination strategies that can be used in prevention as well as therapeutically to combat unwanted immunity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Two approaches to immunological intervention in tumor-host interactions in mouse models are discussed in this review. The first is described with reference to experiments in which CD8(+) T lymphocytes are used to kill established transplantable tumors. Peptides and their optimal presentation by dendritic cells and intervention in immune regulatory mechanisms are the key issues for efficient induction of T-killer cell-mediated tumor eradication. The time frame of tumor therapy and the threat imposed by tumor growth in transplantable models and cancer patients require the induction of a robust T-cell reaction. Prevention of the progression of small preneoplastic lesions, on the other hand, requires the significant and prolonged immune protection sought in the second approach. This is based on antibody production and the coordinated activation of multiple low-avidity cell-mediated mechanisms elicited by DNA vaccination in genetically modified cancer-prone mice, transgenic for a mutant Her-2/neu growth factor receptor expressed at the plasma membrane surface of preneoplastic mammary gland epithelial cells. Vaccination with appropriate DNA formulations results in prolonged immune inhibition of the progression of preneoplastic mammary lesions but is ineffective against established tumors. The use of molecularly defined adjuvants and intervention in immune regulatory mechanisms are critical in both the elicitation of an effective T-cell mediated reaction required for tumor debulking in the first set of models and the induction by vaccination of a sustained immune memory able to prevent the expansion of preneoplastic lesions in genetically cancer-prone mice.

Malaria affects the lives of hundreds of millions of people. Drug therapy is becoming less effective, a vaccine has yet to be developed, and one to two million children die annually as a result of malaria. In the last 10 years, however, there has been great progress towards a vaccine. A number of important antigens have been cloned, including the circumsporozoite (CS) protein which covers the sporozoite and which is a target for antibody and cytotoxic T lymphocytes. In laboratory models, successful vaccination has been achieved with some CS constructs. Although successful immunization with irradiated sporozoites has been achieved in the laboratory, the lack of immunity following natural exposure to sporozoites in endemic countries is puzzling. Parasite variation, host genetic factors and immunological tolerance may each contribute to this situation. Identification of other important antigens and a better understanding of host immune responses to sporozoite and liver stage antigens should be important steps towards rational vaccine design.

Recent developments, in both animal systems and human trials, have provided encouraging results to counter the pessimism that has prevailed concerning the likelihood of obtaining an effective AIDS vaccine. This review summarizes these findings and their impact on defining and focusing the research agenda for the immediate future.