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Richard C. Duggleby

Other affiliations: Anthony Nolan
Bio: Richard C. Duggleby is an academic researcher from University College London. The author has contributed to research in topics: Cell therapy & Immunotherapy. The author has an hindex of 2, co-authored 2 publications receiving 38 citations. Previous affiliations of Richard C. Duggleby include Anthony Nolan.

Papers
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Journal ArticleDOI
TL;DR: The practicalities of making Tregs a viable cell therapy are reviewed, discussing the challenges faced in isolating and manufacturing TregS and defining what are the most appropriate applications for this new therapy.
Abstract: Regulatory T cells (Tregs) are CD4+ T cells that are key players of immune tolerance. They are powerful suppressor cells, able to impact the function of numerous immune cells, including key effectors of inflammation such as effector T cells. For this reason, Tregs are an ideal candidate for the development of cell therapy approaches to modulate immune responses. Regulatory T cell (Treg) therapy has shown promising results so far, providing key knowledge on the conditions in which these cells can provide protection and demonstrating that they could be an alternative to current pharmacological immunosuppressive therapies. However, a more comprehensive understanding of their characteristics, isolation, activation, and expansion is needed to be able design cost effective therapies. Here we review the practicalities of making Tregs a viable cell therapy, in particular, discussing the challenges faced in isolating and manufacturing Tregs and defining what are the most appropriate applications for this new therapy.

52 citations

Journal ArticleDOI
23 Oct 2020-PLOS ONE
TL;DR: Epigenetic assessment offers significant advantages over flow cytometry for analysing cryopreserved CB; similar cell numbers were observed both in fresh and frozen samples, and multiple epigenetic assessments can be performed from DNA extracted from small cryop Reserved CB segments; often the only CB sample available for clinical studies.
Abstract: Background Allogeneic haematopoietic cell transplantation (HCT) is a curative therapy for severe haematological disorders. However, it carries significant risk of morbidity and mortality. To improve patient outcomes, better graft selection strategies are needed, incorporating HLA matching with clinically important graft characteristics. Studies have shown that the cellular content of HCT grafts, specifically higher ratios of T regulatory (Tregs)/T cells, are important factors influencing outcomes when using adult peripheral blood mobilised grafts. So far, no equivalent study exists in umbilical cord blood (CB) transplantation due to the limitations of cryopreserved CB samples. Study design and methods To establish the most robust and efficient way to measure the Treg content of previously cryopreserved CB units, we compared the enumeration of Treg and CD3+ cells using flow cytometry and an epigenetic, DNA-based methodology. The two methods were assessed for their agreement, consistency and susceptibility to error when enumerating Treg and CD3+ cell numbers in both fresh and cryopreserved CB samples. Results Epigenetic enumeration gave consistent and comparable results in both fresh and frozen CB samples. By contrast, assessment of Tregs and CD3+ cells by flow cytometry was only possible in fresh samples due to significant cell death following cryopreservation and thawing. Conclusion Epigenetic assessment offers significant advantages over flow cytometry for analysing cryopreserved CB; similar cell numbers were observed both in fresh and frozen samples. Furthermore, multiple epigenetic assessments can be performed from DNA extracted from small cryopreserved CB segments; often the only CB sample available for clinical studies.

3 citations


Cited by
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Book ChapterDOI
01 Jan 2005
TL;DR: Compare your culture to one of the cultures discussed in this unit, and list as many similarities and differences between the two as you can think of.
Abstract: Compare your culture to one of the cultures discussed in this unit. On a sheet of paper, list the cultures you are comparing and make one column titled “similarities,” and a second column titled “differences.” Now, list as many similarities and differences between the two as you can think of. Are there more similarities or differences between the two cultures you selected? Have you ever met anyone from this culture? How can you use this information to build greater respect between cultures?

1,000 citations

Journal ArticleDOI
TL;DR: The biology of Treg cells is discussed and new efforts in Treg cell engineering to enhance specificity, stability, functional activity and delivery are described to encourage the clinical use of adoptive TReg cell therapy for non-immune diseases, such as neurological disorders and tissue repair.
Abstract: Cellular therapies using regulatory T (Treg) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and graft-versus-host disease. In this Review, we discuss the biology of Treg cells and describe new efforts in Treg cell engineering to enhance specificity, stability, functional activity and delivery. Finally, we envision that the success of Treg cell therapy in autoimmunity and transplantation will encourage the clinical use of adoptive Treg cell therapy for non-immune diseases, such as neurological disorders and tissue repair. Therapies based on adoptive cellular transfer of regulatory T (Treg) cells are currently undergoing clinical trials for autoimmune diseases, graft-versus-host disease and the prevention of transplant rejection. This Review provides an overview of Treg cell biology and discusses the latest approaches to enhance Treg cells for therapeutic purposes.

301 citations

Journal ArticleDOI
TL;DR: Current knowledge and recent developments in immune checkpoint-based therapies for the treatment of hepatocellular carcinoma and cholangiocarcinoma are summarized and the mechanisms underlying its effects are clarified.
Abstract: Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan. Preclinical and clinical studies show immune checkpoint therapy provides survival benefit for greater numbers of patients with liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, two main primary liver cancers. The combination of anti-PD-1/PD-L1 with anti-CTLA-4 antibodies is being evaluated in phase 1, 2 or 3 trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. In addition, studies on activating co-stimulatory receptors to enhance anti-tumor immune responses have increased our understanding regarding this immunotherapy in liver cancer. Epigenetic modulations of checkpoints for improving the tumor microenvironment also expand our knowledge of potential therapeutic targets in improving the tumor microenvironment and restoring immune recognition and immunogenicity. In this review, we summarize current knowledge and recent developments in immune checkpoint-based therapies for the treatment of hepatocellular carcinoma and cholangiocarcinoma and attempt to clarify the mechanisms underlying its effects.

226 citations

Book
30 Sep 1997
TL;DR: A novel component of the European Research Area will require national funders' cooperation in order to be considered for inclusion in the EU Research Area.
Abstract: A novel component of the European Research Area will require national funders' cooperation.

182 citations

Journal ArticleDOI
TL;DR: The actual mechanisms for Th17 cells plasticity to Th1‐like Th 17 cells are discussed and reviewed in association to the role that Th1-like Th17 Cells have on inflammatory and autoimmune disorders.

104 citations