Current Methodology Advances in Cell Therapy Applications

Dear Colleagues,

Cell Therapy per definition uses cellular material that is injected or transplanted into a patient with the aim of treating a disease. Cell Therapy approaches are naturally diverse. Approaches can use autologous (i.e., patient self-derived) material or allogeneic cells (derived from either genetically matched donors or from engineered stem cells). One prominent and well-studied example of Cell Therapy applications are autologous CAR T therapies, where patient T cells are genetically engineered to express specific tumor-targeting chimeric antigen receptors. CAR T therapies have proven to be an efficient treatment for a variety of hematologic cancers. Alternatively, stem cell-derived allogeneic therapies use genetically engineered human stem cells or human-induced pluripotent stem cells that will later be differentiated into the desired effector cells, ensuring a much wider target range. Such allogeneic therapy will provide almost unlimited material and can be applied to a larger number of patients. Cell-based therapies are a rapidly developing field with high medical interest. Cell Therapy development uses cutting-edge techniques that are constantly optimized in several fields: generation of appropriate cell sources, genetic engineering of donor cells, differentiation protocols for stem cell-based products and aspects of safety studies, and rigorous quality assurance procedures for Cell Therapy products.

This Special Issue of Methods and Protocols wants to bridge all these efforts and to collect recent advances in methods, procedures, and protocols for all areas of Cell Therapy applications. We are very much looking forward to receiving your invaluable contributions.

Dr. Kejin Hu
Dr. Lucia Monaco
Dr. Philip Hublitz
Guest Editors

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• cell therapy
• autologous
• allogeneic
• stem cell-based therapies
• T cell engineering
• immuno-oncology
• tissue repair

Title: Enhanced effect of combined αllbβ3 and αvβ3 antagonists in a dual β3-expressing cell line model
Authors: Amal A Elsharif, Laurence H Patterson, Steven D Shnyder, Helen M Sheldrake
Affiliation: Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, BD7 1DP, United Kingdom
Abstract: Several of the integrin family of cell adhesion receptors have been popular targets for the development of anticancer agents, but with little clinical effect to date. Cancer cells usually express multiple redundant integrins; one hypothesis for the lack of efficacy of current antagonists is their high selectivity for a single integrin. This study has investigated the effect of dual β3 antagonism in cancer using known β3 antagonists GR144053 and cRGDfV in to characterise a dual αllbβ3/αvβ3-expressing functional model. We have established that treatment of K562 chronic myeloid leukemia cells with phorbol 12-myristate 13-acetate (PMA) 0.04 μM for 40 h significantly increased the expression of functional αllbβ3 and αvβ3, providing a dual-β3 expressing cell line model suitable for use in adhesion and detachment assays. Combination of αllbβ3 and αvβ3 antagonists synergistically increased their effects on cell adhesion and detachment compared to the use of selective αllbβ3 and αvβ3 antagonists as single agents. Keywords: Integrin αvβ3, αIIbβ3, K562, PMA, cell-based functional assay