CRISPR-based gene disruption and integration of high-avidity, WT1-specific T cell receptors improve antitumor T cell function.

T cell receptor (TCR)-based therapy has the potential to induce durable clinical responses in patients with cancer by targeting intracellular tumor antigens with high sensitivity and by promoting T cell survival. However, the need for TCRs specific for shared oncogenic antigens and the need for manufacturing protocols able to redirect T cell specificity while preserving T cell fitness remain limiting factors. By longitudinal monitoring of T cell functionality and dynamics in 15 healthy donors, we isolated 19 TCRs specific for Wilms' tumor antigen 1 (WT1), which is overexpressed by several tumor types.

Variants of the ADRB2 Gene in COPD: Systematic Review and Meta-Analyses of Disease Risk and Treatment Response.

The β-adrenergic receptor (ADRB) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB function could increase disease risk or reduce the response to endogenous and inhaled adrenergic agonists in COPD. We performed a systematic review and three meta-analyses to assess whether three functional variants (Thr164Ile, Arg16Gly, and Gln27Glu) in the ADRB gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β-agonists in COPD.

New insights into androgenic immune regulation.

Androgens negatively affect both central and peripheral immunity. Their potent immunosuppressive ability is thought to lead to gender dimorphism in autoimmune and infectious disease and hamper immunosurveillance of tumors. Therefore, we investigated the molecular underpinnings of androgens suppression of T-cell differentiation and found evidence that developing strategies to counteract these inhibitory effects may foster successful cancer immunotherapy in the future.

Development of a peptide-based vaccine targeting TMPRSS2:ERG fusion-positive prostate cancer.

Identification of novel vaccine targets is critical for the design and advancement of prostate cancer (PCa) immunotherapy. Ideal targets are proteins that are abundant in prostate tumors while absent in extra-prostatic tissues. The fusion of the androgen-regulated TMPRSS2 gene with the ETS transcription factor ERG occurs in approximately 50 % of prostate cancer cases and results in aberrant ERG expression.