Activated immune cells expressing this construct expanded indefinitely in a feedback loop, without the need for exogenous IL In vitro , immune cells expressing this chimeric protein showed cytotoxicity comparable to or higher than wild-type IL The construct also led to better anticancer effects and superior survival in mouse models. A small subset of NK cells are able to lyse multiple target cells in a consecutive fashion, elicit faster and stronger lytic responses, and replenish their cytokine stores. These cells have become known as serial killers. The chimeric construct also conferred resilience to TGF-beta1, which is secreted by cancer-associated fibroblasts and other cells in the tumor microenvironment and inhibits the anticancer responses of immune cells.
Targeting BB with agonistic antibodies has demonstrated potent antitumor effects in murine tumor models, making this a promising approach for treating cancer through stimulation of the immune system. Two BB agonistic antibodies are currently in the clinic, and while one of these is a much better agonist than the other, it also causes toxicity that is likely related to its potent activation of BB. This has created ongoing interest in developing new therapeutic agonists that have activity that is selective and sufficient to elicit a therapeutic effect while avoiding any on-target toxicity.
The crystal structure of the ligand-receptor complex that Dr. Baca and colleagues solved showed that BBL formed a canonical bell-shaped trimer, which is typical of TNF superfamily member ligands, and also revealed the precise details of how the ligand engages three copies of the receptor, a necessary prerequisite for activation of BB signaling. Foster et al. T cells generated with nucleoside-modified and purified CAR mRNA also showed reduced expression of checkpoint regulators and a differential pattern of genetic activation compared to those made with conventional mRNA.
In vivo studies using a leukemia mouse model revealed that the most robust fold suppression of leukemic burden was achieved using T cells electroporated with purified mRNAs regardless of their nucleoside modification. Log in to leave a comment. This site uses Akismet to reduce spam. Learn how your comment data is processed.
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Breaking tolerance: improving cancer immunotherapy
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Breaking tolerance: improving cancer immunotherapy
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MUM and FA contributed in conception, preparation, review and editing of the manuscript. All authors read and approved the final manuscript. Correspondence to Fotis Asimakopoulos. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions. Search all BMC articles Search. Abstract Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies.