Weekly Digests

2017

June

A therapeutic T cell receptor mimic antibody targets tumor-associated PRAME peptide/HLA-I antigens

June 28, 2017

In a quest to find a highly specific, off-the-shelf cancer immunotherapy, Chang et al. designed and analyzed Pr20, a T cell receptor mimic (TCRm) antibody targeting HLA-A2 complexed with an epitope derived from the tumor-associated antigen PRAME, and presented proof of concept that TCRm antibodies have therapeutic potential in several human cancers. PRAME...

Role of CD28 in PD-1-mediated inhibition and the rescue of exhausted T cells during PD-1-targeted therapy

June 21, 2017

Although the PD-1-targeted therapies have provided clinical benefit in a variety cancers, the mechanism behind PD-1-mediated inhibition of T cells, and their subsequent rescue with PD-1-targeted therapy, is not well understood. In two separate studies, Kamphorst et al. and Hui et al. demonstrate that the CD28 costimulatory pathway plays a surprisingly important role...

Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer

June 14, 2017

BRCA1 is a DNA repair gene that is commonly mutated in breast cancer patients and these tumors often exhibit a “triple negative” phenotype that limits the efficacy of several common therapies. Although cisplatin is somewhat effective as a chemotherapy against BRCA1-mutated breast cancer, the rates of drug resistance and relapse are still fairly...

Chromatin states define tumour-specific T cell dysfunction and reprogramming

June 7, 2017

It is well known that tumor-specific CD8+ T cells (TST) found within solid tumors are often dysfunctional and do not affect tumor progression. TST become dysfunctional early on in the tumorigenesis process and exhibit the same characteristics as tumor-reactive tumor-infiltrating lymphocytes (TILs) in late-stage human solid tumors. Philip et al. hypothesized that the dysfunctional state...