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.

Human T cells engineered with a leukemia lipid-specific TCR enables donor-unrestricted recognition of CD1c-expressing leukemia / Consonni, M.; Garavaglia, C.; Grilli, A.; de Lalla, C.; Mancino, A.; Mori, L.; De Libero, G.; Montagna, D.; Casucci, M.; Serafini, M.; Bonini, C.; Haussinger, D.; Ciceri, F.; Bernardi, M.; Mastaglio, S.; Bicciato, S.; Dellabona, P.; Casorati, G.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 12:1(2021), pp. 4844-4858. [10.1038/s41467-021-25223-0]

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

Grilli A.;Bonini C.;Ciceri F.;Bicciato S.;
2021

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.
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Human T cells engineered with a leukemia lipid-specific TCR enables donor-unrestricted recognition of CD1c-expressing leukemia / Consonni, M.; Garavaglia, C.; Grilli, A.; de Lalla, C.; Mancino, A.; Mori, L.; De Libero, G.; Montagna, D.; Casucci, M.; Serafini, M.; Bonini, C.; Haussinger, D.; Ciceri, F.; Bernardi, M.; Mastaglio, S.; Bicciato, S.; Dellabona, P.; Casorati, G.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 12:1(2021), pp. 4844-4858. [10.1038/s41467-021-25223-0]
Consonni, M.; Garavaglia, C.; Grilli, A.; de Lalla, C.; Mancino, A.; Mori, L.; De Libero, G.; Montagna, D.; Casucci, M.; Serafini, M.; Bonini, C.; Haussinger, D.; Ciceri, F.; Bernardi, M.; Mastaglio, S.; Bicciato, S.; Dellabona, P.; Casorati, G.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1252755
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