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Samuel E.R.,University College London | Newton K.,University College London | Newton K.,Cell Medica | MacKinnon S.,University College London | Lowdell M.W.,University College London
British Journal of Haematology

Cytomegalovirus (CMV) infections post-haematopoietic stem cell transplantation (HSCT) can be effectively controlled through the adoptive transfer of donor-derived CMV-specific T cells (CMV-T). Current strategies involve a second leukapheresis collection from the original donor to manufacture CMV-T, which is often not possible in the unrelated donor setting. To overcome these limitations we have investigated the use of a small aliquot of the original granulocyte-colony stimulating factor (G-CSF) mobilized HSCT graft to manufacture CMV-T. We explored the T cell response to CMVpp65 peptide stimulation in G-CSF mobilized peripheral blood mononuclear cells (PBMC) and subsequently examined isolation of CMV-T based on the activation markers CD154 and CD25. CD25+ enriched CMV-T from G-CSF mobilized PBMC contained a higher proportion of FoxP3 expression than non-mobilized PBMC and showed superior suppression of T cell proliferation. Expanded CMV-T enriched through CD154 were CD4+ and CD8+, demonstrated a high specificity for CMV, secreted cytotoxic effector molecules and lysed CMVpp65 peptide-loaded phytohaemagglutinin-stimulated blasts. These data provide the first known evidence that CMV-T can be effectively manufactured from G-CSF mobilized PBMC and that they share the same characteristics as CMV-T isolated in an identical manner from conventional non-mobilized PBMC. This provides a novel strategy for adoptive immunotherapy that abrogates the need for successive donation. © 2012 Blackwell Publishing Ltd. Source

Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 1.07M | Year: 2009

Cell Medica, develops, manufactures and provides cellular immunotherapy products for the treatment of infectious disease and cancer. Cell Medica Ltd collaborated with eXmoor Pharma Concepts Ltd and University College London (UCL) on this project, with the aim of the development of a scaled-up manufacturing process for production of virus specific T cell therapies. Cell Medica’s lead product is Cytovir CMV, a T cell therapy targeting Cytomegalovirus (CMV) in patients who have undergone bone marrow transplants or allogeneic haematopoietic stem cell transplants (allo-HSCT). The project developed new cell processing methods and achieved step change improvements in the key production parameters of cost, time, quality and flexibility. A modular closed cell processing system was developed and manufacturing costs savings were identified. An advanced manufacturing system was designed and successfully prototyped. A transition plan and supporting documentation is in place to enable Cell Medica to operate within a facility that will support production targets of 5,000+ cell products per annum. eXmoor Pharma Concepts have gained insight and understanding into individualised cellular therapy manufacturing issues and this will allow their support of the development of processes by other groups in the UK and hence the consulting activities of eXmoor. UCL were able evaluate selection of target cells from mobilised aphaeresis, evaluate alternative cell selection targets and develop identity and potency assays, forming a significant part of the UCL researcher’s PhD.

A complex comprising a Class II HLA-DRB1*03 or Class II HLA-DRB1*13 molecule bound to a peptide, wherein the peptide comprises the amino acid sequence HTYTIDWTKDAVTWS or a portion thereof, or a variant of the given amino acid sequence or portion wherein the side chains of one or two or three or four or five or six or seven of the amino acid residues are altered, wherein the peptide comprising the portion, or variant, is capable of binding HLA-DRB1*03 and/or HLA-DRB1*13. The complex may be used to select

Cell Medica | Date: 2012-12-12

An in vitro expansion process for rapid expansion of antigen specific T cells, such as allogeneic antigen specific T cells comprising the steps culturing in a gas permeable vessel a population of PBMCs (such as allogeneic PBMCs) in the presence of antigen, for example a peptide or peptide mix relevant to a target antigen(s), in the presence of an exogenous cytokine characterized in that the expansion to provide the desired population of T cells is 14 days or less, for example 9, 10, 11 or 12 days, such as 10 days. The disclosure also extends to T cell populations generated by and obtained from the method and the use of same in therapy.

The present disclosure provides a method of treating a human patient in need thereof with immune reconstitution therapy by administering a therapeutically effective amount of therapeutic T cell population selected and/or expanded from a mobilised blood sample or a mobilised apheresis sample, wherein selection is on the basis of a steady state marker and/or an activation marker optionally followed by expansion, or expansion is in the presence of antigen, such as a viral antigen. It also extends to methods of generating said therapeutic T cell populations and the product obtainable therefrom.

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