Biotechnology journal
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Biotechnology journal · Jan 2021
ReviewProduction, Processing, and Characterization of Synthetic AAV Gene Therapy Vectors.
Over the last two decades, gene therapy vectors based on wild-type Adeno-associated viruses (AAV) are safe and efficacious in numerous clinical trials and are translated into three approved gene therapy products. Concomitantly, a large body of preclinical work has illustrated the power and potential of engineered synthetic AAV capsids that often excel in terms of an organ or cell specificity, the efficiency of in vitro or in vivo gene transfer, and/or reactivity with anti-AAV immune responses. ⋯ To illustrate the breadth of this portfolio, two chimeric capsids are used as representative examples that are derived through forward- or backwards-directed molecular evolution, namely, AAV-DJ and Anc80. Collectively, this ever-expanding arsenal of technologies promises to facilitate the development of the next AAV vector generation derived from synthetic capsids and to accelerate their manufacturing, and to thus boost the field of human gene therapy.
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Biotechnology journal · Apr 2013
ReviewConvergent mechanisms in pluripotent stem cells and cancer: implications for stem cell engineering.
Stem cells and cancer cells share certain characteristics, including the capacity to self-renew, differentiatie, and undergo epithelial-to-mesenchymal transition (EMT). The mechanisms underlying tumorigenesis retain similarities with processes in normal stem cell development. Comprehensive analysis and comparison of cancer cell and stem cell development will advance the study of cancer progression, enabling development of effective strategies for cancer treatment. ⋯ Next, we detail how stem cell engineering is able to mimic in vivo microenvironments. These efforts can help better identify stem cell-cancer cell interactions, elucidated dysregulated pluripotent signaling pathways occurring in cancer, revealed new factors that restrict tumorigenesis and metastasis potential, and reprogrammed cancer cells to a less aggressive phenotype. The potential of stem cell engineering to enhance cancer research is tremendous and may lead to alternative therapeutic options for aggressive cancers.
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Cancer is the second leading cause of death in the industrialized world. Most cancer patients are treated by a combination of surgery, radiation and/or chemotherapy. Whereas the primary tumor can, in most cases, be efficiently treated by a combination of these standard therapies, preventing the metastatic spread of the disease through disseminated tumor cells is often not effective. ⋯ Whereas passive antibody therapy relies on the repeated application of large quantities of tumor antigen-specific antibodies, active immunotherapy aims at the generation of a tumor-specific immune response combining both humoral and cytotoxic T cell effector mechanisms by the host's immune system following vaccination. In the first part of this review, concurrent developments in active and passive cancer immunotherapy are discussed. In the second part, the various approaches for the production of optimized monoclonal antibodies used for anti-cancer vaccination are summarized.