Preclinical experiments have shown this successfully, as reviewed in Glienke et al.

4–6 In a similar way, both autologous and allogeneic natural killer (NK) effector cells, 7 as well as the NK cell line NK-92, can be redirected against cancer. 2, 3 In addition, a broad range of different cancer target antigens under clinical investigation using CAR-expressing T cells redirected against CD20, CD30, CD138, c-Met, EGFRvIII, ErbB2, FAB, GD2, HER2, WT1, PSMA, NY-ESO1, and others have been reviewed. Long-term remission in those patients with B cell malignancies has been observed. 1, 2 Clinical Phase I/II studies have shown the successful treatment with autologous T cells redirected against CD19 leukemic cells by using recombinant chimeric antigen receptors (CARs), which consist of a single-chain variable fragment (scFv) linked to intracellular signaling domains. S ignificant progress has been made in the last decade by using redirected immune response against advanced cancer, especially for leukemia. The robustness of the process and the constant quality of the final product in a closed and automated system give rise to improve harmonized manufacturing protocols for engineered T cells in future gene therapy studies. In-process control also demonstrated sufficient glucose levels during automated feeding and medium removal. In the GFP run, the transduction efficacy was 83%.

Most important in the split product, a very similar expansion curve was reached comparing the overall freshly CD62L selected cells with those after thawing, which could be demonstrated in the T cell subpopulations as well by showing a nearly identical conversion of the CD4/CD8 ratio. Expression of CD62L was downregulated on T cells after thawing, which led to the decision to purify CD62L +CD3 + T cells freshly with cryopreservation thereafter. Starting with 0.5 × 10 8 purified CD3 + T cells, three mock runs and one run including transduction with green fluorescent protein (GFP)-containing vector resulted in a median final cell product of 16 × 10 8 T cells (32-fold expansion) up to harvesting after 2 weeks. Naïve and central memory T cells from apheresis products were first immunomagnetically enriched using anti-CD62L magnetic beads and further processed freshly ( n = 3) or split for cryopreservation and processed after thawing ( n = 1). Therefore, this study addresses the proof of principle in clinical-scale selection, stimulation, transduction, and expansion of T cells using the automated closed CliniMACS ® Prodigy system. The continuously increasing interest in those advanced gene therapy medicinal products (GTMPs) leads to a manufacturing challenge regarding automation, process robustness, and cell storage.

Multiple clinical studies have demonstrated that adaptive immunotherapy using redirected T cells against advanced cancer has led to promising results with improved patient survival.

Texmacs medium