Successful isolation and expansion of CMV‐reactive T cells from G‐CSF mobilized donors that retain a strong cytotoxic effector function. (9th October 2012)

• Record Type: Journal Article
• Authors: Samuel, Edward R.; Newton, Katy; Mackinnon, Stephen; Lowdell, Mark W.
• Is Part Of: British journal of haematology. Volume 160:Number 1(2013:Jan.)
• Page Start: 87
• Page End: 100
• Publication Date: 2012-10-09
• Subjects: haematopoietic stem cell transplantation -- granulocyte‐colony stimulating factor mobilization -- cytomegalovirus‐specific T cells -- CD154 -- immunotherapy; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12082
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: 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.