Angioimmunoblastic T cell Lymphoma (AITL) is a rare cancer, which has no curative treatment. We recently generated a transgenic mouse model, which developed a CD4⁺ follicular T cell-like lymphoma, mimicking AITL (Mondragón et al., Cancer Cell, 2019). In the case of AITL the malignant driver cell is a T cell and more specifically a CD4⁺ T cell. Chimeric Antigen Receptor (CAR) T cells seems to emerge as a promising technique for cancer therapies especially for leukemia and lymphomas. Therefore, we developed as a new therapeutic option for AITL, a CD8-targeted lentiviral vector (LV) that allows anti-CD4 CAR expression only by CD8⁺ T cells. It is of utmost importance to target exclusively the CD8⁺ T cell population for expression of the CAR to avoid malignant T cell induction. For CD8 recognition, an agonistic CD8-specific single-chain variable fragment was displayed at the vector surface, allowing a specific recognition of CD8⁺ T cells. Moreover, to avoid life-long immunosuppression, the CAR construct is co-expressing a safety switch, to permit CAR T cell elimination in vivo. We showed here that CD8⁺ T cell transduction is specific and the expression of the CAR induced CD4⁺ T cell death in murine splenocytes in vitro. Additionally, in immunocompetent mice, we were able to confirm targeted expression in CD8⁺ cells upon direct intravenous injection of the CD8-LV. Currently, we are exploring the specificity and efficacy of CD8 targeted LVs encoding the anti-CD4 CAR in vivo in WT mice and in our new AITL preclinical mouse model.