CARAMBA(T-CURX)

Fusarium head blight (FHB) is one of the most important diseases of durum, spring, and winter wheat in Canada. Growers rely on an integrated strategy to manage the disease, including fungicide application at the current recommendation of early to 50% anthesis (BBCH61–65). This study evaluated the effect of fungicide application timing and seeding rates of durum wheat on FHB. Field trials were carried out from 2016 to 2018 at three locations in Saskatchewan. Eight treatments of the metconazole fungicide Caramba were applied to durum seeded at 75 and 400 seeds m−2. The fungicide treatments consisted of a nontreated check, a treated check, and applications at BBCH59, BBCH61, BBCH65, BBCH69, and BBCH73 and a dual application treatment (BBCH61 followed by BBCH73). FHB index, proportion of Fusarium-damaged kernels (%FDK), deoxynivalenol (DON), grain protein content (GPC, %), and yield were evaluated. Seeding rates influenced all parameters. The high seeding rate had a higher yield and FHB index but lower DON and GPC than did the lower seeding rate. All fungicide treatments resulted in lower FHB index, DON, and %FDK than the nontreated check. Under FHB conducive conditions, all anthesis applications from BBCH61 to BBCH69 had a similar effect on FHB index, %FDK, DON, and yield, whereas in years with low disease severity, the application at BBCH65 had lower FHB index, %FDK, and DON relative to other single applications. The dual application (BBCH61 + 73) treatment resulted in similar FHB index levels, %FDK, and DON content as the BBCH65 application at all site years. Our results indicate that the window of fungicide application can be extended to the end of flowering when FHB risk is high.

Clinical development of chimeric antigen receptor (CAR)-T-cell therapy has been enabled by advances in synthetic biology, genetic engineering, clinical-grade manufacturing, and complex logistics to distribute the drug product to treatment sites. A key ambition of the CARAMBA project is to provide clinical proof-of-concept for virus-free CAR gene transfer using advanced Sleeping Beauty (SB) transposon technology. SB transposition in CAR-T engineering is attractive due to the high rate of stable CAR gene transfer enabled by optimized hyperactive SB100X transposase and transposon combinations, encoded by mRNA and minicircle DNA, respectively, as preferred vector embodiments. This approach bears the potential to facilitate and expedite vector procurement, CAR-T manufacturing and distribution, and the promise to provide a safe, effective, and economically sustainable treatment. As an exemplary and novel target for SB-based CAR-T cells, the CARAMBA consortium has selected the SLAMF7 antigen in multiple myeloma. SLAMF7 CAR-T cells confer potent and consistent anti-myeloma activity in preclinical assays in vitro and in vivo. The CARAMBA clinical trial (Phase-I/IIA; EudraCT: 2019-001264-30) investigates the feasibility, safety, and anti-myeloma efficacy of autologous SLAMF7 CAR-T cells. CARAMBA is the first clinical trial with virus-free CAR-T cells in Europe, and the first clinical trial that uses advanced SB technology worldwide.