The annals of cancer treatment clearly show that chemotherapy, surgery, and radiotherapy are dominantly used as ultimate therapeutic options for cancer patients. These conventional treatments are replete with critical side effects and have low response and survival rates. For this reason, oncological research is experiencing a fast pace of improvement that multiple promising therapeutic options have emerged, including but not limited to adoptive T-cell therapy, targeted therapy, induced pluripotent stem cells (iPSCs) technology, and genome editing system. Over the last decade, each of these cutting-edge therapeutic techniques has received remarkable attentions among clinicians and researchers as a new treatment option for cancer patients, despite being at preliminary stage of development.
Adoptive T-cell therapy, using patient’s autologous or allogenic T cells to express either novel T cell receptors (TCRs) or chimeric antigen receptors (CARs), has shown a clinically feasible approach in treatment of cancer patients. Consequently, the United States Food and Drug Administration (FDA) approved five types of CAR-T cell therapies for hematologic malignancies, including Idecabtagene vicleucel (Abecma), Lisocabtagene maraleucel (Breyanzi), Brexucabtagene autoleucel (Tecartus), Tisagenlecleucel (Kymriah), and Axicabtagene ciloleucel (Yescarta). However, despite successful treatment outcomes such as observing complete and durable responses in patients with late-stage diseases, or even in some cases cure, this therapy seems to be ineffectual in some patients. New constructive strategies and approaches are required to address challenges that prevent the success of adoptive T-cell therapy from entering the clinical settings or market.
iPSCs are somatic cells that have been reprogrammed through introducing reprogramming factors, such as Oct3/4, Sox2, Klf4, c-Myc, Nanog, and Lin28. This novel technology opens a new avenue for cancer treatment by which researchers can study disease mechanisms and develop disease models to work further on therapeutics development in a way that were not possible before. iPSCs technology is at early stage of development and there are not much clinical trials or successful pre-clinical studies. Hence, more preclinical studies particularly under Good Laboratory Practice (GLP) are needed to be investigated to pave the way for clinical purposes.
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system is a new genome editing technology. Genome editing refers to the delivery of an editing machinery system in cells of interest to modify their genome through either the replacement of faulty genes or insertion of new genes to treat diseases or boost the therapeutic outcomes. CRISPR/Cas9 system received a huge popularity among researchers due to its distinct advantages. To date, this genome editing technology has been very helpful for the success of both adoptive T-cell therapy and iPSCs technology and other genebased therapies. Interestingly, CRISPR/Cas9 has addressed critical challenges associated with current therapeutic options, such as reducing side effects of cell therapy, making genetically modified-T cells resistant to suppressive molecules, generating off-the-shelf products especially from iPSC-derived cells and allogenic sources, and providing the opportunity to screen genes responsible for defect or success of the products.
With this research topic, we aim to focus on newly emerged therapeutic platforms, especially adoptive T cell therapy, iPSCs technology, and CRISPR/Cas9 system. We would like to discuss current challenges within these therapeutic approaches that prevent them from entering the realm of clinical trials and why they have been discontinued or terminated from pre-clinical or clinical studies. Interestingly, the combination of these new therapeutic approaches provides a multitude of opportunities and leads us to a new era of therapy. For example, iPSC-derived T cells undergo genome editing process to become an unlimited off-the-shelf T cell product and then genetically engineered to express chimeric receptors, as a universal product for third-party patients. Thus, shedding more lights on these therapeutic options may bring a new revolutionary means of treatment to cancer patients.
In this Research Topic we welcome authors submitting Original research, Review, Mini-Review, Perspective, and Clinical trials articles. The subtopics covered in this Research Topic are, but not limited to:
• Novel strategies that address pre-clinical and clinical challenges in each of these therapeutic approaches, iPSCs, CRISPR/Cas9, and adoptive T-cell therapy
• Studies concerning the combination of iPSCs, CRISPR/Cas9, and adoptive T-cell therapy
• Novel manufacturing process for iPSCs and adoptive T-cells development, a budget-friendly approach
• Efficient gene delivery system based on non-viral methods (using nanoparticles or mRNA, etc.)
• Combination therapy with one of these therapeutic approaches
• Analysis of genetic/epigenetic changes related to the iPSCs and genetically engineered-T cells
• Clinical studies for iPSCs, CRISPR/Cas9, and adoptive T-cell therapy
We would like to acknowledge and credit
Dr. Muhammad Sadeqi Nezhad as Topic Coordinator, having organized and contributed to the preparation of the proposal for this Research Topic.
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Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.