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  • While a large number of clinical trials have been

    2019-06-12

    While a large number of clinical trials have been completed or underway, there is a lack of strong evidence of their effectiveness and safety. Some experts pointed out that autologous transplantation may put patients at a risk of receiving the genetically defective immune cells, while allogeneic transplantation has a potential to cause myeloablation [35]. Moreover, recent studies stated that cultured MSC may undergo transdifferentiation into proinflammatory candesartan cilexetil in the chronic inflammatory environment. Yasuhiro et al. [48] first demonstrated that MSCs secreted IL-7 and play a candesartan cilexetil pathological role in IBD by forming the niche for colitogenic CD4 memory T cells in bone marrow. More researches are needed to further understand the mechanisms of stem cells before they enter clinical application. We still do not know what kind of stem cells is best for CD. In addition to HSCs and MSCs, amniotic fluid stem cells have been used and the results were encouraging [49]. IFN-γ-treated human amniotic fluid stem cells could inhibit T-cell proliferation and increase CD4(+) CD25(+) FOXP3(+) regulatory T cells. In vivo, IFN-γ-treated human amniotic fluid stem cells were capable of immunoregulatory function, promoting allograft survival in a mouse model of allogeneic skin transplantation. Thus, amniotic fluid stem cells may be a new source of stem cells for immunotherapy.
    Conclusion Stem cell therapy is a field that has developed considerably in the past decade. Currently available clinical data indicates that stem cell therapy for CD is very promising. In spite of the huge accomplishments, stem cell-based therapy is still in its infancy. There are only 2 ongoing Phase III trials using stem cells for the treatment of CD (Table 5). However, there is a long way to go before they are officially approved to be used for CD. Further large randomized trials are warranted. Enormous advances are needed to bridge the translational gap between the benchtop researches and clinical applications of stem cells for CD.
    Author contributions
    Conflict of interest
    Introduction Multiple myeloma (MM) is a fatal plasma cell neoplasm affecting one to five per 100,000 individuals and constitutes the second most common hematological malignancy [1]. Despite the application of auto/allo-hematopoietic stem cell transplantation and the development of many new agents, such as bortezomib, thalidomide, and lenalidomide, MM yet currently remains incurable. The vast majority of MM patients continue to suffer from relapses that are refractory to chemotherapy based on immunomodulatory drugs (IMiD) and proteasome inhibitors. The prognosis of such patients is very poor, with a median overall survival of nine months and an event-free survival of just five months [2]. Therefore, it is urgent to find novel approaches for patients with chemotherapy-resistant and advanced MM. Ongoing studies with monoclonal antibodies could potentially expand the armamentarium against myeloma and could foster significant advances in the field. CD138 is highly expressed on MM cells and is involved in their development and/or proliferation [3], making CD138 an attractive therapeutic target [4–8]; however, the clinical benefit of anti-CD138 therapy without immunoconjugate is very limited. Clinical trial reports of labeled radioimmunotherapies, such as iodine-131 anti-CD138 monoclonal antibody (mAb), have suggested that CD138-directed cytotoxicity therapy may be a clinically effective approach and is at least an alternative therapeutic strategy, especially for those patients refractory to chemotherapy and with progressive MM [9]. The adoptive transfer of genetically engineered immune effecter cells aims to rapidly establish T cell-mediated tumor immunity. In this approach, the patient\'s own T cells are targeted to tumor cells through a transgene-encoded antigen receptor consisting of either chains or a chimeric antigen receptor (CAR) [10]. When expressed in T cells, CARs efficiently redirect T cell specificity and cytotoxicity to cells expressing the targeted antigen in an HLA-independent manner. The CARs used in these experiments contained T cell activation domains from molecules such as CD3ζ and a variety of costimulatory domains, such as those from CD28 and 4-1BB. Recently accumulated clinical trial data have demonstrated that genetically modified T cells with CAR against CD19 or CD20 provide promising therapeutic strategies for leukemias and lymphomas [11–14]. These reports prompted us to initiate a pilot clinical trial on the treatment with autologous T cells expressing an anti-CD138 chimeric antigen receptor (CART138) for MM patients. This study is registered at clinicaltrials.gov as #NCT01886976. To date, five patients have been treated. Here, we report the feasibility and clinical response of in vivo T cell treatment with CD138-directed CAR in MM patients.