About this Research Topic
These biological “living drugs” are produced by isolating patient’s T lymphocytes from peripheral blood mononuclear cells (PBMCs) and engineering these T cells with either gamma-retroviral (RV) or lentiviral (LV) vectors that encode for either TCRs or CARs. However, their clinical grade manufacturing is complex, requiring good manufacturing practice (GMP) facilities, a long timeline for engineering the cellular product and the availability of patient PBMCs of good quality. Serious side effects and adverse events, including cytokine release syndrome (CRS) and neurologic problems, represent additional major issues that have been documented in CAR-T cell treated patients. The experience thus far gained in this field by the principle clinical centers developing these types of clinical studies has led to strategies to control and, in most cases, even resolve these adverse events. However, further studies on the mechanisms involved in these adverse reactions and how to avoid them will grant important advances in the efficacy and safety of engineered T cells. Moreover, dose, phenotype, tumor burden, the design of receptors and their expression and the choice of target antigens are critical points that require ad hoc investigations.
In order to provide patients with immediate treatment, several groups have designed various strategies to obtain donor-derived allogeneic “off-the-shelf” CAR-T cells, with a few clinical studies already ongoing for patients with hematological malignancies. Gene editing platforms (e.g., CRISPR/CAS-9 or TALEN) to knock-out specific gene(s), such as TCR and HLA, are under development to overcome CAR-T cell-mediated graft-versus-host disease (GvHD) or host versus graft reactions, respectively. However, this approach still needs to be optimized in terms of manufacturing, reduction of the risk of toxicities and selection of the target genes.
This Research Topic will collect selected contributions in the following topics:
• The clinical evolution of CAR-T cell therapy.
• Targeting tumors with TCR engineered T lymphocytes.
• Optimizing the choice of target molecules and in vivo models for engineered T lymphocytes.
• Manufacturing implementation of engineered T cells and Pharma/Biotech perspectives.
• Allogeneic/”Off the Shelf” Therapy with CAR-T cells.
• Innovative approaches to improve the targeting of cancer cells.
• Regulatory and quality aspects of building clinical centers for advanced therapy medicinal products.
Contributors are welcome to submit Original Research, Method, Mini-review and Review articles related to the topics mentioned above and covered in the 1st International Workshop on Engineered Immune Cells in Cancer Immunotherapy (EICCI), held at Sidra Medicine in Doha, Qatar, on 15th-16th February 2019EICCI Workshop.
Topic Editor Dr. Francisco Martin Molina is the founder of LentiStem Biotech, a Start-up focused on the development of SAFER AND MORE EFFICIENT gene delivery systems for gene-cell therapy applications with special focus on lentiviral vectors and its applications to the genetic correction of rare disorders and cancer immunotherapy. Topic Editor Prof. Cameron Turtle receives financial support from Juno Therapeutics and Nektar Therapeutics. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.