Targeting colorectal cancer cells using AND-gated adaptor RevCAR T-cells.

Despite the success of chimeric antigen receptor (CAR) T-cells especially for treating hematological malignancies, critical drawbacks, such as "on-target, off-tumor" toxicities, need to be addressed to improve safety in translating to clinical application. This is especially true, when targeting tumor-associated antigens (TAAs) that are not exclusively expressed by solid tumors but also on hea9lthy tissues. To improve the safety profile, we developed switchable adaptor CAR systems including the RevCAR system.

Presymptomatic Reduction of Individuality in the App Knockin Model of Alzheimer's Disease.

Background: One-third of the risk for Alzheimer's disease is explained by environment and lifestyle, but Alzheimer's disease pathology might also affect lifestyle and thereby impair the individual potential for health behavior and prevention.

Methods: We examined in mice how the App (NL-F) knockin mutation affects the presymptomatic response to environmental enrichment (ENR) as an experimental paradigm addressing nongenetic factors. We assessed the emergence of interindividual phenotypic variation under the condition that both the genetic background and the shared environment were held constant, thereby isolating the contribution of individual behavior (nonshared environment).

Targeting Acute Myeloid Leukemia Using the RevCAR Platform: A Programmable, Switchable and Combinatorial Strategy.

Clinical translation of novel immunotherapeutic strategies such as chimeric antigen receptor (CAR) T-cells in acute myeloid leukemia (AML) is still at an early stage. Major challenges include immune escape and disease relapse demanding for further improvements in CAR design. To overcome such hurdles, we have invented the switchable, flexible and programmable adaptor Reverse (Rev) CAR platform.