Autologous cell therapy has proven to be an effective treatment for hematological malignancies. Cell therapies for solid tumors are on the horizon, however the high cost and complexity of manufacturing these therapies remain a challenge. Routinely used open steps to transfer cells and reagents through unit operations further burden the workflow reducing efficiency and increasing the chance for human error. Here we describe a fully closed, autologous bioprocess generating MAGE-B2 TCR-T cells. This bioprocess yielded 5 – 12e9 MAGE-B2-specific TCR-expressing T cells, transduced at low MOIs, within 7 to 10 days, and cells exhibited an enriched memory T cell phenotype and enhanced metabolic fitness. It was demonstrated that activating, transducing, and expanding leuko-apheresed cells in a single bioreactor without a T cell enrichment step promoted lentivirus transduction efficiency while resulting in comparable level of T cell purity (~97%) as that of leukopak cells that went through CD8+ and CD4+ positive selection. The critical process parameters of the bioreactor, including culturing at a high cell density (7e6 cells/mL), adjusting rocking agitations during phases of scale up, lowering glycolysis through addition of 2-Deoxy-D-glucose (2-DG), and modulating IL-2 levels, were shown to positively regulate TCR expression and cell doubling time, and promote resistance to effector-associated apoptosis of TCR-T cells. The bioprocess described herein supports scale-out feasibility by enabling processing of multiple patients’ batches in parallel within a Grade C cleanroom.