title: T cells raised against allogeneic HLA-A2/CD20 kill primary follicular lymphoma and acute lymphoblastic leukemia cells.
abstract: T cells mediating a graft-versus-leukemia/lymphoma effects without causing graft-versus-host disease would greatly improve the safety and applicability of hematopoietic stem cell transplantation. We recently demonstrated that highly peptide- and HLA-specific T cells can readily be generated against allogeneic HLA-A*02:01 in complex with a peptide from the B cell-restricted protein CD20. Here, we show that such CD20-specific T cells can easily be induced from naïve precursors in cord blood, demonstrating that they do not represent cross-reactive memory cells. The cells displayed high avidity and mediated potent cytotoxic effects on cells from patients with the CD20(pos)  B cell malignancies follicular lymphoma (FL) and acute lymphoblastic leukemia (ALL). However, the cytotoxicity was consistently lower for cells from two of the ALL patients. The ALL cells that were less efficiently killed did not display lower surface expression of CD20 or HLA-A*02:01, or mutations in the CD20 sequence. Peptide pulsing fully restored the levels of cytotoxicity, indicating that they are indeed susceptible to T cell-mediated killing. Adoptive transfer of CD20-specific T cells to an HLA-A*02:01(pos)  patient requires an HLA-A*02:01(neg) , but otherwise HLA identical, donor. A search clarified that donors meeting these criteria can be readily identified even for patients with rare haplotypes. The results bear further promise for the clinical utility of CD20-specific T cells in B cell malignancies.
authors.affiliation: Institute of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Ingerid Weum
authors.initials: IW
authors.lastname: Abrahamsen
authors.forename: Synneva
authors.initials: S
authors.lastname: Kjellevoll
authors.forename: Margrethe
authors.initials: M
authors.lastname: Greve-Isdahl
authors.forename: Nadia
authors.initials: N
authors.lastname: Mensali
authors.forename: Sébastien
authors.initials: S
authors.lastname: Wälchli
authors.forename: Shraddha
authors.initials: S
authors.lastname: Kumari
authors.forename: Beate Fossum
authors.initials: BF
authors.lastname: Loland
authors.forename: Torstein
authors.initials: T
authors.lastname: Egeland
authors.forename: Arne
authors.initials: A
authors.lastname: Kolstad
authors.forename: Johanna
authors.initials: J
authors.lastname: Olweus
mesh_terms: D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D006087:Graft vs Host Reaction / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D018951:Antigens, CD20; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen