Transient anti-BCMA CAR T-cells for Treatment of Multiple Myeloma

ABSTRACT Multiple myelomaMMclaims overlives globally each yearAlthough several new therapies have been approved over the past decadevirtually all patients relapse and the median survival remains at onlyyearsThe depth of therapeutic response correlates with time to relapseand eradicating tumor cells early in the disease process may be necessary to achieve clinical cureA potentially curative approach is autologous cell therapy with chimeric antigen receptorCART cells redirected to a target antigenFor MMan attractive target antigen is B cell maturation antigenBCMAan antigen marker with extremely high sensitivity and specificity for myeloma and plasma cellsExperiments proposed in this SBIR will define a transientlyexpressed anti BCMA CAR product that will overcome the toxicities generated by permanently modified TcellsThe goals of the Specific Aims are toreduce immunogenicity of transiently expressedmRNAantiBCMA CAR T cells to target MM in vitrooptimize T cell activation domains for the RNA based CAR constructoptimize translation and degradation of the mRNA transcript in T cellsanddemonstrate antiBCMA CAR T cell function in two in vivo models of MMSuch transient expression allows for predictable and controllable treatment of myeloma and may enable CAR T cell therapy to be used in patients with early diseasewith vastly improved potential of achieving clinical cure NARRATIVE Cellular immunotherapy has shown remarkable responses in patients with certain cancersincluding multiple myelomaUnfortunatelyin their current formcell therapies are often toxic and reserved for use only for patients with advanced diseaseData generated from the proposed research may allow a powerful new cell therapy to be used in patients with less advanced multiple myelomawith vastly increased chances of a cure