Discriminatory Power of Combinatorial Antigen Recognition in Cancer T Cell Therapies.

Precise discrimination of tumor from normal tissues remains a major roadblock for therapeutic efficacy of chimeric antigen receptor (CAR) T cells. Here, we perform a comprehensive in silico screen to identify multi-antigen signatures that improve tumor discrimination by CAR T cells engineered to integrate multiple antigen inputs via Boolean logic, e.g., AND and NOT. We screen >2.5 million dual antigens and ∼60 million triple antigens across 33 tumor types and 34 normal tissues. We find that dual antigens significantly outperform the best single clinically investigated CAR targets and confirm key predictions experimentally. Further, we identify antigen triplets that are predicted to show close to ideal tumor-versus-normal tissue discrimination for several tumor types. This work demonstrates the potential of 2- to 3-antigen Boolean logic gates for improving tumor discrimination by CAR T cell therapies. Our predictions are available on an interactive web server resource (antigen.princeton.edu).

Failure of Permethrin-Treated Military Uniforms to Protect Against a Laboratory-Maintained Knockdown-Resistant Strain of Aedes aegypti.

Military forces and the recreational industry rely on the repellent properties of permethrin-treated fabrics and N,N-diethyl-meta-toluamide (deet)-based lotions to provide protection from disease vectors and hematophagous organisms. Concerns regarding efficacy have been raised as pyrethroid resistance becomes more common and recent publications present contradictory conclusions. In this preliminary study, consenting volunteers were exposed to pyrethroid-susceptible and pyrethroid-resistant Aedes aegypti strains while wearing sleeves of untreated or permethrin-treated army uniform fabric as well as with untreated or deet-treated exposed forearms. Deet was nearly 100% effective against both susceptible and resistant strains. However, permethrin treatment provided no significant protection against the resistant Puerto Rico strain relative to untreated control sleeves. These results confirm that pyrethroid-resistant vectors can negate the efficacy of permethrin-treated uniforms. Additional testing with resistant field strains is needed to better understand the risk to service members.