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The recent years have seen a wave of adoptive cell therapies (ACTs), a type of immunotherapy in which T cells (T cell transfer therapy) and other immune cells are obtained from patients, activated and multiplied outside the body, and infused in larger numbers back into the blood circulation to help fight cancers. 
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BigField GEG Tech's insight:
Gene engineering company Cellectis may present potentially crucial data on its UCART19 immuno-oncology treatment at the upcoming American Society of Hematology meeting.
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BigField GEG Tech's insight:
The scientists detected hemizygous deletions spanning the CD19 locus and de novo frameshift and missense mutations in exon 2 of CD19 in some relapse samples. Using genome editing, they demonstrated that exon 2 skipping bypasses exon 2 mutations in B-ALL cells and allows expression of the N-terminally truncated CD19 variant, which fails to trigger killing by CART-19 but partly rescues defects associated with CD19 loss. Thus, this mechanism of resistance is based on a combination of deleterious mutations and ensuing selection for alternatively spliced RNA isoforms.
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BigField GEG Tech's insight:
Here, the scientists have examined anti-leukemia potency of CART-cells targeting CD19 antigen using second generation CAR containing CD28-costimulatory domain cloned into piggyBac-transposon vector and patient-derived chemoresistant paediatric acute lymphoblastic leukaemia. Co-culture of leukaemia cells with bone marrow stroma cells reduced target cell loss suggesting that leukaemia cell mobilization into circulation may help to remove the protective effect of bone marrow stroma and increase the efficacy of CART-cell therapy.
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T-cell transfer therapies have not yet been successfully applied to solid tumors because T cells do not readily penetrate and persist in solid tumor masses for long periods of time, and because their activity is attenuated by an immunosuppressive tumor microenvironment. One way to overcome these limitations could be to couple T cell transfer therapies with cytokine therapy. However, a serious drawback of this approach is the significant side effects resulting from cytokines circulating freely in the body, leading to toxicity and potentially fatal inflammatory syndromes. Now, researchers have developed a nanotechnology-based solution to these problems. The method uses an unnatural sugar that is absorbed and embedded in the outer coating of T cells, which can then be used to anchor cytokines. The concentrated cytokines improve T-cell function locally without producing unwanted systemic side effects. In mice with melanoma, the approach also stimulated the host immune system against tumor cells, which inhibited tumor growth. As an adjunct to CAR-T cell therapy, it resulted in complete regression of lymphoma tumors at otherwise non-curative cell doses.