Transfection of CD4(+) and CD8(+) T cells with mRNA encoding recombinant immunoreceptors for use in cancer immunotherapy

We explored for the first time transfection of CD4(+) and CD8(+) T cells with mRNA encoding recombinant immunoreceptors for use in the adoptive immunotherapy of cancer and obtained data from this study.

CD4(+) and CD8(+) T cells were efficiently transfected with immunoreceptors specific for ErbB2 and CEA. The immunoreceptor expression was transient with half-maximal expression at day 2 and no detectable immunoreceptor expression at day 9 after electroporation. Immunoreceptor-transfected T cells were specifically activated upon coincubation with ErbB2(+) and CEA(+) tumor cells, respectively, resulting in secretion of interferon-gamma (IFNgamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNFalpha). Furthermore, immunoreceptor-transfected CD8(+) T cells specifically lysed ErbB2(+) and CEA(+) tumor cells, respectively. The RNA-transfected T cells retained their cytotoxic function after 2 days of activation and exhibited cytolytic activities like retrovirally transduced T cells. Opposed to standard procedures using retroviral gene transduction to constitutively express immunoreceptors in T cells, transient immunoreceptor expression by RNA transfection should minimize the risk of persistence of potential autoaggression.

created over 15 years ago (22 February 2010)    last modified over 12 years ago (29 April 2013)   [ RDF ]   [ RelFinder ]