Weekly Digests

2019

June

4-1BB agonism that only works on site

June 26, 2019

4-1BB plays an important role in the costimulation of T cells and is an attractive target for immunotherapy, however, clinical targeting of 4-1BB using agonistic antibodies has been plagued by either low potency or off-target liver toxicity due to Fcγ receptor (FcγR)-mediated cross-linking. To overcome these challenges and induce tumor-localized T cell costimulation...

Tumor infiltration is governed by CCL5 and CXCL9

June 19, 2019

Patients whose tumors are strongly infiltrated by immune cells tend to have a better prognosis and better responses to immunotherapy, but the mechanisms that underlie immune infiltration are not clearly defined. To better understand the infiltration of T cells into tumors, Dangaj et al. investigated the roles of chemokines in the tumor microenvironment...

Tregs eat costimulatory ligands to prevent T cell activation

June 12, 2019

It is well-known that Tregs suppress T cell responses to self-peptides via the CTLA-4 pathway in order to maintain normal immune homeostasis, but the details of this mechanism have not been fully elucidated. In vitro studies have shown that Tregs suppress the CD28-dependent activation of naive T cells by limiting their access to...

Multispecific antibodies set the rules of engagement for NK cell-mediated tumor control

June 5, 2019

Many bispecific T-cell engager antibodies have been developed and tested in recent years, but challenges with off-target toxicities and lack of efficacy against solid tumors remain. Instead of targeting T cells for antitumor immunity, Gauthier et al. designed and developed trifunctional NK-cell engagers (NKCEs) with the goal of reducing off-target cytotoxicity and enabling...

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