![]() Clinical trials demonstrated high response rates of BCMA CAR T cells as well, but median progression-free survival was shorter than for CD19 CAR T cells. 1, 2, 3, 4 The second most frequently targeted antigen is the B cell maturation antigen (BCMA), which is broadly expressed in multiple myeloma. The clinical application of second-generation chimeric antigen receptor (CAR) T cells targeted at the CD19 antigen on B cell neoplasm has shown remarkable response rates ranging from 50% to 85% depending on the B cell malignancy, followed by extended disease-free and overall survival rates. Together, adaptation of a standard CliniMACS Prodigy protocol to low input numbers resulted in efficient retroviral transduction with a high CAR T cell yield. Strong cell proliferation yielded cell numbers sufficient for clinical application, while effector functions were maintained. Cultivation in the presence of IL-7/IL-15 enabled the harvest of CAR T cells containing an increased CD4 + T SCM fraction and 70% T SCM cells amongst CD8 +. ![]() Although starting with only 15% of standard T cell input, the selected T SCM/T CM material was efficiently activated and transduced with a BCMA CAR-encoding retrovirus. A CliniMACS Prodigy process was combined with flow cytometry-based enrichment of CD62L +CD95 + T cells. We designed a clinically compliant protocol for generating BCMA CAR T cells starting with increased T SCM/T CM cell input. ![]() Long-lived, self-renewing multipotent T memory stem cells (T SCM) and T central memory cells (T CM) likely sustain superior tumor regression, but their low frequencies in blood from cancer patients impose a major hurdle for clinical CAR T production. A leading cause of CAR T cell failure is their lack of expansion and limited persistence. A simple optimal control problem is used to illustrate the functionality of the IDOS server and the completeness of our language DOML.The advent of CAR T cells targeting CD19 or BCMA on B cell neoplasm demonstrated remarkable efficacy, but rapid relapses and primary refractoriness remains challenging. The paper describes some constructs of DOML language which enable such chaining of solvers. In particular one can get a crude approximation to a solution of his problem by applying one solver and then continue solving the problem by another solver which gives a more accurate solution but may require a better initial guess than the first solver. Then, once defined, the problem can be attempted by different solvers. In result, a user can describe his problem in a programming-language-independent way. The aim of the project was to develop a prototype, online-accessible environment for solving dynamic optimization problems.Within the project we also constructed a modeling language (Dynamic Optimization Modeling Language, DOML) for defining optimal control problems. Development and deployment of the Interactive Dynamic Optimization Server is a result of a project funded by NCBiR (National Center for Research and Development in Poland). ![]() This paper presents a newly deployed server, IDOS (Interactive Dynamic Optimization Sever), devoted to solving optimal control problems. The paper presents the workings of the server, the modelling language proposed (DOML) and an example of a problem specified in DOML and solved with IDOS. As a result, a user can specify his problem in a programming-language-neutral manner and use the server to attempt to solve it. One of the goals of the project was also to propose a modelling language (Dynamic Optimization Modelling Language, DOML) for defining optimal control problems – in a way that would not depend on constructs borrowed from concrete (lower level) programming languages. The aim of the project was to develop a prototype, online-accessible environment providing the service of solving dynamic optimization problems. Development and deployment of the Interactive Dynamic Optimization Server is a result of a project funded by NCBiR (National Center for Research and Development in Poland) under grant R02-0009-06 (henceforth called briefly the IDOS project). This paper presents a newly deployed server, Interactive Dynamic Optimization Server (IDOS), devoted to solving optimal control problems.
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