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T cells raised against allogeneic HLA‐A2/CD20 kill primary follicular lymphoma and acute lymphoblastic leukemia cells
Author(s) -
Abrahamsen Ingerid Weum,
Kjellevoll Synneva,
GreveIsdahl Margrethe,
Mensali Nadia,
Wälchli Sébastien,
Kumari Shraddha,
Loland Beate Fossum,
Egeland Torstein,
Kolstad Arne,
Olweus Johanna
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26209
Subject(s) - cd20 , cytotoxic t cell , immunology , adoptive cell transfer , leukemia , hematopoietic stem cell transplantation , cancer research , lymphoma , transplantation , biology , medicine , t cell , immune system , in vitro , biochemistry
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.