Human T cells engineered with a leukemia lipid-specific TCR enables donor-unrestricted recognition of CD1c-expressing leukemia

Michela Consonni, Claudio Garavaglia, Andrea Grilli, Claudia de Lalla, Alessandra Mancino, Lucia Mori, Gennaro De Libero, Daniela Montagna, Monica Casucci, Marta Serafini, Chiara Bonini, Daniel Häussinger, Fabio Ciceri, Massimo Bernardi, Sara Mastaglio, Silvio Bicciato, Paolo Dellabona, Giulia Casorati

Research output: Contribution to journalArticlepeer-review

Abstract

Acute leukemia relapsing after chemotherapy plus allogeneic hematopoietic stem cell transplantation can be treated with donor-derived T cells, but this is hampered by the need for donor/recipient MHC-matching and often results in graft-versus-host disease, prompting the search for new donor-unrestricted strategies targeting malignant cells. Leukemia blasts express CD1c antigen-presenting molecules, which are identical in all individuals and expressed only by mature leukocytes, and are recognized by T cell clones specific for the CD1c-restricted leukemia-associated methyl-lysophosphatidic acid (mLPA) lipid antigen. Here, we show that human T cells engineered to express an mLPA-specific TCR, target diverse CD1c-expressing leukemia blasts in vitro and significantly delay the progression of three models of leukemia xenograft in NSG mice, an effect that is boosted by mLPA-cellular immunization. These results highlight a strategy to redirect T cells against leukemia via transfer of a lipid-specific TCR that could be used across MHC barriers with reduced risk of graft-versus-host disease.

Original languageEnglish
Article number4844
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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