Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by the accumulation of immature myeloid cells. Current treatments often fail to achieve durable remission, underscoring the need for innovative therapeutic approaches. CD97 is a cell surface protein with broad, increased expression on AML cells compared to normal blood stem and progenitor cells. Moreover, CD97 overexpression in AML patients has been associated with poor survival, thus emerging as a potential therapeutic target.
Hepatocellular carcinoma (HCC) is a fatal cancer and the third cause of cancer-related deaths worldwide. Current therapies have focused on CAR T cells for treating HCC. Glypican-3 (GPC3) is a membrane protein that is overexpressed in HCC but not in healthy adult liver tissue, thus becoming a promising therapeutic target for HCC management.
To address the various limitations of traditional CAR T therapy in autoimmune disease, Sail Biomedicines Inc. has developed an in vivo CAR T platform that enables in vivo transient programming of patient immune cells.
Ovarian cancer remains a leading cause of cancer-related deaths among women, with high recurrence rates and resistance to chemotherapy. CAR T-cell therapies present limited efficacy in solid tumors due to tumor heterogeneity and immune suppression in the tumor microenvironment.
CAR T-cell therapy for B-cell malignancies has still to be improved regarding durability, manufacturing complexity or toxicity, among others. Precigen Inc. has presented data regarding the preclinical development and efficacy of PRGN-3008, a PD-1-expression inhibitor cell therapy targeting CD19 that was built in a next-generation ultra CAR T platform.
A study has demonstrated the potential of a novel ligand-based CAR T-cell therapy for targeting CD7-positive T-cell malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphomas. The receptor CD7 is a prominent target antigen, being expressed in around 95% of T-ALL, 50% of peripheral T-cell lymphomas and 10% of acute myeloid leukemias.
Although CD19-directed CAR T cells can initially induce remission in 70-90% of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), post-CAR relapses are frequent. These relapses are driven by insufficient persistence of CAR T cells, allowing for antigen-positive B-ALL re-emergence and loss of the targeted epitope either in isolation or as part of lineage-switching.
Although CAR T-cell therapies have reached significant clinical success in hematological malignancies, their utility in solid tumors remains limited. One of the main challenges is the scarcity of truly cancer-specific antigens for precise targeting of solid tumors. The use of engineered small, specific antigen-binding domains, such as nanobodies, could be a potential strategy to improve the specificity and efficacy of CAR T cells against solid tumors.
Allogenica SAS has been awarded a €2.5 million (US$2.7 million) grant under the French government’s France 2030 program to help advance its universal CAR T candidate, XL-001, for CD19-positive hematologic cancers.
A team at Baylor College of Medicine conducted research to identify novel cell-surface cancer/germline antigens (CGAs) expressed in triple-negative breast cancer (TNBC) that could serve as targets for development of CAR T therapies against this disease.
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