Concise Review: Human Pluripotent Stem Cells to Produce Cell-Based Cancer Immunotherapy

Abstract

Human pluripotent stem cells (PSCs) provide a promising resource to produce immune cells for adoptive cellular immunotherapy to better treat and potentially cure otherwise lethal cancers. Cytotoxic T cells and natural killer (NK) cells can now be routinely produced from human PSCs. These PSC-derived lymphocytes have phenotype and function similar to primary lymphocytes isolated from peripheral blood. PSC-derived T and NK cells have advantages compared with primary immune cells, as they can be precisely engineered to introduce improved anti-tumor activity and produced in essentially unlimited numbers. STEM CELLS 2018;36:134-145 SIGNIFICANCE STATEMENTHuman pluripotent stem cells provide an important strategy to produce immune cells that can better target and treat refractory cancers.

An improved method to produce clinical scale natural killer cells from human pluripotent stem cells

“…Cell-based therapies for treatment of relapsed/refractory cancers have been gaining in interest and importance. In addition to studies using CAR-T cells, clinical trials using NK cells isolated from peripheral blood or umbilical cord blood have been rapidly expanding 13 . However, these sources of NK cells are difficult to engineer and vary from donor to donor.…”

“…However, these sources of NK cells are difficult to engineer and vary from donor to donor. iPSC-derived NK cells are being translated to clinical trials to now provide a standardized, "off-the-shelf" therapy that can be routinely engineered to target and better treat relapsed/refractory malignancies 13 . The improved method allows efficient, rapid and reproducible production of hESC-/iPSC-NK cells from different pluripotent stem cell lines without the requirement of time-consuming single cell adaption process thus facilitate clinical scale production and translation of hESC/iPSC-NK cells.…”

“…To date, most of NK cell-based adoptive immunotherapy clinical trials have used primary NK cells isolated from donor's peripheral blood (PB-NK cells) 9, 10 , umbilical cord blood (UCB-NK cells) 11 or the transformed NK cell line NK-92 12 . While each have demonstrate clinical efficacy, there are some shortcomings 13 . For example, PB-NK cells and UCB-NK cells are typically a heterogeneous mix of NK cells and other immune cells that can vary from donor to donor 14 .…”

Application of iNKT Cell-targeted Active Immunotherapy in Cancer Treatment

“…Many researchers have explored the possibility of cancer immunotherapy using iNKT cells, that is an attractive tool to activate both innate and adaptive immunity. Although novel treatments including induced pluripotent stem (iPS) cells, chimeric antigen receptors, biphasic antibodies, and nanotechnology are being developed one after another (10,11), this review focuses on iNKT cell-targeted active immunotherapy.…”

Now More Than Ever: The Importance of Reporting Evidence-Based Science

“…Among our most downloaded and cited articles for 2018 were several outstanding concise reviews, which are an excellent way to get "up to speed" in a specific field. The topics included Cell Therapy for Critical Limb Ischemia [6], Clinical Application of Chimeric Antigen Receptor T Cell Therapies [7], Human Pluripotent Stem Cells to Produce Cell-Based Cancer Immunotherapy [8], Age-Related Clonal Hematopoiesis [9], Wnt Signaling Pathways in Skin Development [10], Three-Dimensional Organoids as Preclinical Models [11], Assessing the Genome Integrity of Human Induced Pluripotent Stem Cells [12], Stem Cell-Based Therapy in Myocardial Repair [13], and The Use of Stem Cells for Understanding and Treating Huntington's Disease [14]. These concise reviews are from experts in their respective fields and cite evidence-based research, helping to move the respective fields forward in a reliable manner.…”