Anticancer cellular immunotherapies derived from umbilical cord blood

Balassa, Katalin; Rocha, Vanderson

doi:10.1080/14712598.2018.1402002

Cited by 18 publications

(17 citation statements)

References 126 publications

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“…Given the reported advantages of CBNK and CAR-NK cells, 14 , 48 , 49 we further tested whether the 221-mIL-21 feeder expansion system could also expand CB-derived CAR-NK cells. To expand CBNK cells ex vivo , unfractionated CB lymphocytes were stimulated for 7 days with 221-mIL-21 feeder cells in the presence of soluble IL-2 and IL-15, inducing rapid proliferation of CBNK cells ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways

Yang

Badeti

Hsiang-Chi

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Clinical success of chimeric antigen receptor (CAR) T cell immunotherapy requires the engineering of autologous T cells, which limits the broader implementation of CAR cell therapy. The development of allogeneic and universal cell products will significantly broaden their application and reduce costs. Allogeneic natural killer (NK) cells can be used for universal CAR immunotherapy. Here, we develop an alternative approach for the rapid expansion of primary NK and CAR-NK cells with superior expansion capability and in vivo cytotoxicity from various sources (including peripheral blood, cord blood, and tumor tissue). We apply a human B-lymphoblastoid cell-line 721.221 (hereinafter, 221)-based artificial feeder cell system with membrane-bound interleukin 21 (mIL-21) to propagate NK and CAR-NK cells. The expansion capability, purity, and cytotoxicity of NK cells expanded with 221-mIL-21 feeder cells are superior to that of conventional K562-mIL-21 feeder cells. RNA sequencing (RNA-seq) data show that 221-mIL-21 feeder cell-expanded NK cells display a less differentiated, non-exhausted, limited fratricidal, memory-like phenotype correlated with enriched metabolic pathways, which explains underlying mechanisms. Thus, “off-the-shelf” NK and CAR-NK cells with superior functionalities and expansion using a genetically modified 221-mIL-21 feeder cell expansion system will greatly support clinical use of NK immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways

Yang

Badeti

Hsiang-Chi

et al. 2020

Molecular Therapy - Methods & Clinical Development

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“…Taking all into account, in this study we aimed at evaluating the efficacy of CAR-NK cells from different cell sources against CD19 expressing leukemic cells. We tested NK cells from adult blood (AB), as well as umbilical cord blood (CB), as studies suggest higher anticancer activity of CB cells compared with other sources, which provides a rationale for the application of CB-derived immunotherapy and cord blood banks uses 35 .…”

Section: Introductionmentioning

confidence: 99%

Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells

Herrera¹,

Santos²,

Vesga³

et al. 2019

Sci Rep

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Among hematological cancers, Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) are the most common leukemia in children and elderly people respectively. Some patients do not respond to chemotherapy treatments and it is necessary to complement it with immunotherapy-based treatments such as chimeric antigen receptor (CAR) therapy, which is one of the newest and more effective treatments against these cancers and B-cell lymphoma. Although complete remission results are promising, CAR T cell therapy presents still some risks for the patients, including cytokine release syndrome (CRS) and neurotoxicity. We proposed a different immune cell source for CAR therapy that might prevent these side effects while efficiently targeting malignant cells. NK cells from different sources are a promising vehicle for CAR therapy, as they do not cause graft versus host disease (GvHD) in allogenic therapies and they are prompt to attack cancer cells without prior sensitization. We studied the efficacy of NK cells from adult peripheral blood (AB) and umbilical cord blood (CB) against different target cells in order to determine the best source for CAR therapy. AB CAR-NK cells are slightly better at killing CD19 presenting target cells and CB NK cells are easier to stimulate and they have more stable number from donor to donor. We conclude that CAR-NK cells from both sources have their advantages to be an alternative and safer candidate for CAR therapy.

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“…Due to the immaturity of the immune system of a new-born, the use of UCB cells for cell therapy does not require matching of genes relating to HLA (Human Leucocyte Antigens) human tissue compatibility, as evidenced by the absence of an acute or chronic form of the disease "graft-versus-host" (graft versus host disease) [13,14]. In addition, with UCB cell transplantation, tumor transformation of cells in the recipient's body is practically prevented [15].…”

Section: Introductionmentioning

confidence: 99%

Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat

Markosyan

Safiullov

Izmailov

et al. 2020

IJMS

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Currently, the main fundamental and clinical interest for stroke therapy is focused on developing a neuroprotective treatment of a penumbra region within the therapeutic window. The development of treatments for ischemic stroke in at-risk patients is of particular interest. Preventive gene therapy may significantly reduce the negative consequences of ischemia-induced brain injury. In the present study, we suggest the approach of preventive gene therapy for stroke. Adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) or gene engineered umbilical cord blood mononuclear cells (UCB-MC) overexpressing recombinant VEGF, GDNF, and NCAM were intrathecally injected before distal occlusion of the middle cerebral artery in rats. Post-ischemic brain recovery was investigated 21 days after stroke modelling. Morphometric and immunofluorescent analysis revealed a reduction of infarction volume accompanied with a lower number of apoptotic cells and decreased expression of Hsp70 in the peri-infarct region in gene-treated animals. The lower immunopositive areas for astrocytes and microglial cells markers, higher number of oligodendrocytes and increased expression of synaptic proteins suggest the inhibition of astrogliosis, supporting the corresponding myelination and functional recovery of neurons in animals receiving preventive gene therapy. In this study, for the first time, we provide evidence of the beneficial effects of preventive triple gene therapy by an adenoviral- or UCB-MC-mediated intrathecal simultaneous delivery combination of vegf165, gdnf, and ncam1 on the preservation and recovery of the brain in rats with subsequent modelling of stroke.

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Anticancer cellular immunotherapies derived from umbilical cord blood

Cited by 18 publications

References 126 publications

Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways

Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways

Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells

Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat

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