Lentiviral vectors (LVs) have been established as the primary alternative for gene therapy due to their ability to achieve permanent integration into both proliferating and quiescent cells. They stand out for its use in the modification of hematopoietic cells for treating several diseases and for the generation of chimeric antigen receptor (CAR)-T cells for cancer immunotherapies.  However, LVs production remains a challenging and costly process, which critically depends on the packaging cell’s ability to resist intrinsic transfection and manipulation related stresses. In this line, we have engineered the gold standard packaging cell line (HEK293T) by knocking out two proapoptotic genes (which we will name X and Y to maintain confidentiality) using the CRISPR-Cas9 system. This has resulted in the development of a novel cell line under patent application process (HEK293T DKO). We first showed that the bulk population of HEK293T-XY-DKO cells exhibited enhanced resistance to apoptosis. Importantly, it also resulted in up to 1.5x higher titers for some LVs, such as those encoding for CARs. Moreover, we demonstrated that the deletion of the proapoptotic genes on the packaging cell did not affect the ability of the CAR LVs to generate fully functional CAR-T cells. Overall, our results here describe a new bulk engineered cell line that could be considered itself as an alternative for producing CAR-encoding LVs with a higher titer but that could also be the first step for further optimization by clonal selection.