Aussie researchers have used CRISPR gene editing tools to “armor” chimeric antigen receptor (CAR) T cells to activate additional cancer-fighting proteins at the tumor site, enabling them to target cancer cells in solid tumors.
Glioblastoma is the most frequent and aggressive primary brain cancer in adults, and patients can expect to live shorter than 2 years, regardless of therapy. The cancer can be treated with CAR T cells, but many patients develop resistance because tumors mutate or delete the antigens recognized by the T cells, while the tumor microenvironment suppresses T-cell activity.
Myrio Therapeutics Pty Ltd. is set to advance lead product PHOX2B PC-CAR T (PHOX2B peptide-centric chimeric antigen receptor autologous T cells) into clinical trials for relapsed neuroblastoma following IND clearance by the FDA. The first patient will be enrolled around mid-year.
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.
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