The efficacy of current CART therapies can be improved through introducing multi domain engineered constructs in the setting of non T cells as well as allogeneic CARTs. This can help target disease with lack of response by the first generation constructs by improving efficiency of targeting and also enhancing the killing capability of the engineered cells. The new generation of CARTs employs clustered regularly.
interspaced short palindromic repeats (CRISPR) technology to knock-out (KO) key components of donor T-cells like T-cell receptor related components, Class I and Class II MHC complex expression and enhance T-cell function, respectively. Additionally AAV vectors can be used to knock in genes that can reduce the risk of graft vs host disease (GVHD) and improve killing of tumor cells.
The CMC considerations for such next generation CARTs would need a robust analytical strategy to develop a selection criteria for healthy donor-derived apheresis materials utilized for clinical manufacturing.to minimize safety risks and make sure of quality of starting material for manufacturing of allogeneic CAR T-cell products. The residual levels of viral vectors or gene editing agents as well as adventitious agents from the donor cells and the variant nonCAR transduced cells will all need to be controlled with a specification and will the mitigation approaches to control these will be discussed in the talk.
Learning Objectives:
Upon completion, participant will be able to learn the challenges from current the autologous CAR-T in commerical operation, and understand new challenges associated with the next generation of CART modalities
Learn how to mitigate such challenges during early process development and mitigate them as much as possible to improve manufacuring success and reduce risks for clinical trials
Understand the technologies that address these challenges
