Cancers have become common human diseases that are involved in uncontrolled cell growth and division. Many signs and symptoms, including cough, bleeding, and fever has been found in various cancer patients. Meanwhile, pilot studies have shown that a wide variety of factors, such as smoking history, viral infections, as well as genetic variations, are associated with the development and progression of cancers.
Up to now, cancers have been classified into over 300 types based on the specific occurrence site. Among them, carcinomas, sarcomas, leukemia, and lymphomas have been considered as main categories of cancers, and they are the cause of approximately 36% of cancer deaths in patients. As a consequence, many attempts have been made to develop the most effective strategies against tumors. For instance, surgery, chemotherapy, and radiation therapy are standard treatments for most cancer patients. Moreover, a wide array of novel cancer therapeutics, such as stem cell therapy, immunotherapy, and drug delivery treatment have been generated for improving the therapeutic effect of cancers in clinical use.
Fig.1 Roadblocks to translating human iPSC technology to the clinic. (Sharkis, 2012)
Induced pluripotent stem cells (iPSCs) are a new group of stem cells derived from different adult somatic cells. In general, the transcription factors, including Oct4, Sox2, and Klf4, of embryonic stem cells (ESCs) have been genetically modified and reprogrammed to form iPSCs. Recent studies have revealed that iPSCs can self-renew indefinitely and differentiate into certain types of cells, such as hepatocytes and hematopoietic cells. As a result, iPSC-based disease therapy has aroused much attention for a large number of disease treatments, like degenerative diseases, blood disorders, and renal diseases. Furthermore, many reports have indicated that iPSC technology has the potential therapeutic applications for treating a variety of cancers, especially for hematological malignancies.
Nowadays, the genetic engineering of iPSCs with adoptive T-cell therapy has been regarded as a new inspiring idea for cancer therapy. For example, different generations of chimeric antigen receptors (CARs) have been engineered by using iPSC technology to produce unlimited T-iPSC clones. The results have illustrated that these iPSC-derived CAR-T cells can strongly inhibit tumor growth in a mice model.
iPSCs play an important role in disease modeling and the development of stem cell therapies against cancers. Till now, many large scale clinical trials of iPSC-derived cell therapy have been conducted on patients with acute myeloid leukemia (AML) or B-cell lymphoma. In a recent study, a random and double-blind phase I/II study of iPSC-based CAR-T cell therapy has been designed and performed on both 48 healthy individuals and 48 AML patients. The data have suggested that multiple doses of T-iPSCs can be easily administered to a patient to trigger durable responses against AML. Besides, iPSC-derived natural killer cells (NKs) cancer immunotherapy has been generated by using multiple anti-tumor properties of iPSCs and NKs to killing B-cell lymphoma. This is the first-of-its-kind that has been approved and used clinically to attack tumors. Consequentially, clinical-scale derivation of different cell types, including NKs, from human iPSCs has opened a whole new door in cancer therapy.
Fig.2 Differentiation of CAR-engineered T-iPSCs into CD19-specific functional T lymphocytes. (Themeli, 2013)
References
For Research Use Only. Not For Clinical Use.
