Cytotoxic T lymphocytes for leukemia and lymphoma

Bollard, Catherine M.; Barrett, A. John

doi:10.1182/asheducation-2014.1.565

Cited by 17 publications

(24 citation statements)

References 36 publications

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“…Polyclonal, virus-specific T cells expanded ex vivo and reinfused into hematopoietic stem cell transplant patients have shown efficacy for the treatment of Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus, BK virus, and human herpesvirus 6 infection [28][29][30][31][32][33][34] as well as the treatment of EBV-mediated malignancies. [35][36][37][38][39] T cells generated using these sophisticated methods of expansion have been safe and well tolerated, as well as highly effective. 38,40 We previously demonstrated that it is feasible to adapt this method of expansion of polyclonal virus-specific T cells to the HIV setting and expand polyfunctional, potent HXTCs targeting multiple HIV epitopes under good manufacturing practice (GMP) conditions.…”

Section: Introductionmentioning

confidence: 99%

HIV-Specific, Ex Vivo Expanded T Cell Therapy: Feasibility, Safety, and Efficacy in ART-Suppressed HIV-Infected Individuals

et al. 2018

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Adoptive T cell therapy has had dramatic successes in the treatment of virus-related malignancies and infections following hematopoietic stem cell transplantation. We adapted this method to produce ex vivo expanded HIV-specific T cells (HXTCs), with the long-term goal of using HXTCs as part of strategies to clear persistent HIV infection. In this phase 1 proof-of-concept study (NCT02208167), we administered HXTCs to antiretroviral therapy (ART)-suppressed, HIV-infected participants. Participants received two infusions of 2 Â 10 7 cells/m 2 HXTCs at a 2-week interval. Leukapheresis was performed at baseline and 12 weeks post-infusion to measure the frequency of resting cell infection by the quantitative viral outgrowth assay (QVOA). Overall, participants tolerated HXTCs, with only grade 1 adverse events (AEs) related to HXTCs. Two of six participants exhibited a detectable increase in CD8 T cell-mediated antiviral activity following the two infusions in some, but not all, assays. As expected, however, in the absence of a latency reversing agent, no meaningful decline in the frequency of resting CD4 T cell infection was detected. HXTC therapy in ART-suppressed, HIV-infected individuals appears safe and well tolerated, without any clinical signs of immune activation, likely due to the low residual HIV antigen burden present during ART.

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Section: Introductionmentioning

confidence: 99%

HIV-Specific, Ex Vivo Expanded T Cell Therapy: Feasibility, Safety, and Efficacy in ART-Suppressed HIV-Infected Individuals

et al. 2018

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“…Interestingly, not only CD8+ tumor-reactive T cells are isolated with this approach, but also effector CD4+ CTLs. Although CD4+ T cells are classically viewed as helper cells facilitating CD8+ T cell function, it is now clear that both cell subsets can exert cytotoxicity against tumor targets ( 3 , 38 ). Moreover, we have demonstrated that by sorting doublet-forming T cells, we are selecting only cytotoxic T cells and depleting regulatory T cells with immune suppressive function from the pool of patient's T cells.…”

Section: Discussionmentioning

confidence: 99%

Selection of Tumor-Specific Cytotoxic T Lymphocytes in Acute Myeloid Leukemia Patients Through the Identification of T-Cells Capable to Establish Stable Interactions With the Leukemic Cells: “Doublet Technology”

et al. 2018

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The relevance of the immune system in cancer has long been studied. Autologous adoptive T cell therapies, based on the use of tumor infiltrating lymphocytes (TILs), have made great progress in recent years for the treatment of solid tumors, especially melanoma. However, further work is needed to isolate tumor-reactive T cells among patients diagnosed with hematologic malignancies. The dynamics of the interaction between T cells and antigen presenting cells (APC) dictate the quality of the immune responses. While stable joints between target cells and T lymphocytes lead to the induction of T cell activation and immune response, brief contacts contribute to the induction of immune-tolerance. Taking advantage of the strong interaction between target cell and activated T-cells, we show the feasibility to identify and isolate tumor-specific cytotoxic T lymphocytes (CTLs) from acute myeloid leukemia (AML) patients by flow cytometry. Using this technology, CTLs bound through T cell receptor (TCR) to tumor cells can be identified in peripheral blood and bone marrow and subsequently selected and isolated by FACS-based cell sorting. These CTLs display higher percentage of effector cells and marked cytotoxic activity against AML blasts. In conclusion, we have developed a new procedure to identify and select specific cytotoxic T cells in patients diagnosed with acute myeloid leukemia.

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“…In the present study, the expression of TLR2 significantly increased following stimulation with rMBP-NAP, which indicated that the secretion of antitumor cytokines from PBMCs possibly depend on the TLR2 signaling pathway. Cytotoxic lymphocytes, which serve an essential role in cancer immunotherapy, have been identified as CD4 + CTL and CD8 + CTL (29). The CD4 + CTLs produce multiple antitumor cytokines, including INF-γ, and facilitate CD8 + T cell activation and differentiation (30).…”

Section: Discussionmentioning

confidence: 99%

Toll‑like receptor agonist rMBP‑NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer

Ding

Zhang

et al. 2018

Oncol Lett

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Toll-like receptor (TLR) agonists are known for their ability to inhibit tumor progression via enhancing antitumor cytokines production and cytotoxic T lymphocyte (CTL) activity. Recombinant Helicobacter pylori neutrophil-activating protein fused with maltose-binding protein (rMBP-NAP) has been reported as a novel TLR agonist for antitumor treatment in murine models. The present study aimed to determine the potential and efficacy of the rMBP-NAP for antitumor treatment prior to further clinical trials. The rMBP-NAP was expressed and purified for subsequent experiments. Peripheral blood mononuclear cells (PBMCs) from health donors and patients with lung cancer (LC) were incubated with PBS and 0.2 mg/ml rMBP-NAP. Antitumor cytokines production was assayed using ELISA and reverse transcription-quantitative polymerase chain reaction analysis. The cytolytic activity of PBMCs and the number of Interferon-γ (IFN-γ)-secreting cells were assayed using lactate dehydrogenase and Enzyme-linked ImmunoSpot assays, respectively. The results from the present study revealed that the expression of IFN-γ, interleukin (IL)-2, tumor necrosis factor-α and IL-12 of PBMCs from patients with LC and healthy donors were significantly increased following treatment with rMBP-NAP (P<0.05). Additionally, rMBP-NAP significantly upregulated the number of IFN-γ-secreting cells in PBMCs and prominently increased the cytotoxic activity of PBMCs (P<0.05). Furthermore, the expression of TLR2 was significantly enhanced following rMBP-NAP stimulation (P<0.05), which indicated that rMBP-NAP may serve an antitumor role via TLR2 signaling pathways. Overall, these results demonstrated that rMBP-NAP possesses the potential to be a novel immunomodulatory candidate drug and requires further evaluation in clinical trials.

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Cytotoxic T lymphocytes for leukemia and lymphoma

Cited by 17 publications

References 36 publications

HIV-Specific, Ex Vivo Expanded T Cell Therapy: Feasibility, Safety, and Efficacy in ART-Suppressed HIV-Infected Individuals

HIV-Specific, Ex Vivo Expanded T Cell Therapy: Feasibility, Safety, and Efficacy in ART-Suppressed HIV-Infected Individuals

Selection of Tumor-Specific Cytotoxic T Lymphocytes in Acute Myeloid Leukemia Patients Through the Identification of T-Cells Capable to Establish Stable Interactions With the Leukemic Cells: “Doublet Technology”

Toll‑like receptor agonist rMBP‑NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer

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