Antitumor immune response of dendritic cells (DCs) expressing tumor‐associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow‐derived DCs. Issue 2 (1st August 2013) - Iwamoto, Hiromitsu
Abstract : It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC‐based immunotherapy. Therefore, we used the induced pluripotent stem (iPS) cell‐derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow‐derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (+) cytotoxic T lymphocytes (CTLs) was assayed using a 51 Cr‐release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100‐specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor‐associated antigen‐specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine. Abstract : What's new? Dendritic cells (DCs) loaded with tumor antigens are important components of immune‐based cancer therapies. However, the limited recovery of bone‐marrow derived DCs from the blood of cancer patients is a serious obstacle to the common use of DC‐based treatments. Here, the authors present an important alternative. They show that DCs derived from induced pluripotent stem cells (iPSCs) are equal in antigen‐presentation and migration properties to bone‐marrow derived DCs. In a model using adenoviral transduction of the gene encoding tumor‐associated antigen, they demonstrate similar antitumor immune responses elicited by both DC types. This new technique may help overcome the limitations of traditional DC‐based therapies and may represent a significant step towards a more effective personalized anticancer medicine.