The Emerging Role of Induced Pluripotent Stem Cells as Adoptive Cellular Immunotherapeutics.
Vedika MehraJyoti Bikram ChhetriSamira AliClaire RoddiePublished in: Biology (2023)
Adoptive cell therapy (ACT) has transformed the treatment landscape for cancer and infectious disease through the investigational use of chimeric antigen receptor T-cells (CAR-Ts), tumour-infiltrating lymphocytes (TILs) and viral-specific T-cells (VSTs). Whilst these represent breakthrough treatments, there are subsets of patients who fail to respond to autologous ACT products. This is frequently due to impaired patient T-cell function or "fitness" as a consequence of prior treatments and age, and can be exacerbated by complex manufacturing protocols. Further, the manufacture of autologous, patient-specific products is time-consuming, expensive and non-standardised. Induced pluripotent stem cells (iPSCs) as an allogeneic alternative to patient-specific products can potentially overcome the issues outlined above. iPSC technology provides an unlimited source of rejuvenated iPSC-derived T-cells (T-iPSCs) or natural killer (NK) cells (NK-iPSCs), and in the context of the growing field of allogeneic ACT, iPSCs have enormous potential as a platform for generating off-the-shelf, standardised, "fit" therapeutics for patients. In this review, we evaluate current and future applications of iPSC technology in the CAR-T/NK, TIL and VST space. We discuss current and next-generation iPSC manufacturing protocols, and report on current iPSC-based adoptive therapy clinical trials to elucidate the potential of this technology as the future of ACT.
Keyphrases
- induced pluripotent stem cells
- cell therapy
- nk cells
- stem cells
- mesenchymal stem cells
- stem cell transplantation
- clinical trial
- bone marrow
- infectious diseases
- end stage renal disease
- newly diagnosed
- ejection fraction
- peripheral blood
- chronic kidney disease
- sars cov
- papillary thyroid
- physical activity
- body composition
- small molecule
- phase ii
- randomized controlled trial
- low dose
- high throughput
- prognostic factors
- squamous cell carcinoma
- squamous cell
- open label
- human health
- single cell
- patient reported
- lymph node metastasis