St. Jude Reference #SJ-19-0050
The treatment of acute myeloid leukemia (AML) is an ongoing challenge due to its high relapse rates and treatment related mortality. Researchers at St. Jude set out to develop a safe and effective immunotherapy strategy for AML, but developing such strategies for AML is particularly difficult due to the marked overlap between antigens expressed on leukemic blasts and normal tissues. They postulated Glucose-regulated-protein 78 (GRP78), which is localized to the endoplasmic reticulum (ER) in healthy tissues, but highly expressed at the cell surface of AML cells might be a good target. A panel of six GRP78 CARs were generated and have demonstrated recognition and killing of GRP78+ AML cells in an antigen specific manner.
The generated CARs can be expressed in other immune cells (for example, γδ T cells, iNKT cells, NK cells, or macrophages). In addition, GRP78 is widely expressed in hematological malignancies and solid tumors, so GRP78-CAR T cells can potentially target a broad range of cancers.
Immunotherapy, acute myeloid leukemia (AML), Glucose-regulated-protein 78 (GRP78), chimeric antigen receptor, CAR, γδ T cells, iNKT cells, NK cells, macrophages, hematological malignancies, solid tumors
Granted patents or published applications
Application published Oct. 28, 2021 as WO 2021/216994
Related scientific references
Hebbar, N., Epperly, R., Vaidya, A. et al. CAR T cells redirected to cell surface GRP78 display robust anti-acute myeloid leukemia activity and do not target hematopoietic progenitor cells. Nat Commun 13, 587 (2022). https://doi.org/10.1038/s41467-022-28243-6
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