The Emerging Role of InVitro-Transcribed mRNA in Adoptive T Cell Immunotherapy.

Abstract

Adoptive Tcell therapy is a form of cellular therapy that utilizes human immune cells, often empowered by the expression of recombinant proteins, to attack selected targets present on tumor or infected cells. Tcell-based immunotherapy has been progressing over the past several decades, and reached a milestone with the recent US Food and Drug Administration (FDA) approval of chimeric antigen receptor Tcell therapy for relapsed and refractory leukemia and lymphoma. Although most studies have used viral vectors, a growing number of researchers have come to appreciate invitro-transcribed (IVT) mRNA for the development, testing, and application of Tcell-based immunotherapeutics. IVT mRNA offers inherent safety features, highly efficient recombinant protein translation, and the ability to control pharmacokinetic properties of the therapy. In this review, we discuss the history of IVT mRNA in adoptive Tcell therapy, from tumor-infiltrating lymphocytes and Tcell receptor-based therapies to chimeric antigen receptor therapy and gene-editing techniques, as well as prior and ongoing clinical trials.