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Formal criminogenic risk tools can be an important control in assessing racial inequities in access to treatment courts and in evaluating both proximal and distal outcomes from those programs. To achieve this potential, however, it is important that risk tools themselves operate in a racially neutral fashion and that they operate consistently over the period assessed. Tools that are not properly calibrated by race and changes in the tools used over the life of a program are therefore significant evaluation concerns. Our paper is the first to assess the adequacy of an important risk-needs instrument, the LSI-R, across racial groups in a drug treatment court setting. The main contribution of the current study is not as a test of that instrument, which has been widely studied in other settings. Rather, because two different criminogenic risk tools were used over the study time period, we took this opportunity to explore the use of a readily constructible "proxy" measure of risk to support analysis of risk and race interactions over the life of the program., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin. Rapamycin withdrawal paused DARIC33-stimulated T cell effector functions, which were restored following reexposure to rapamycin, demonstrating reversible effector function control. While rapamycin-regulated DARIC33 T cells were highly sensitive to target antigen, CD34+ stem cell colony-forming capacity was not impacted. We benchmarked DARIC33 potency relative to CD19 CAR T cells to estimate a T cell dose for clinical testing. In addition, we integrated in vitro and preclinical in vivo drug concentration thresholds for off-on state transitions, as well as murine and human rapamycin pharmacokinetics, to estimate a clinically applicable rapamycin dosing schedule. A phase I DARIC33 trial has been initiated (PLAT-08, NCT05105152), with initial evidence of rapamycin-regulated T cell activation and antitumor impact. Our findings provide evidence that the DARIC platform exhibits sensitive regulation and potency needed for clinical application to other important immunotherapy targets.