Glioblastoma, the most aggressive and lethal form of brain cancer in adults, has long evaded effective treatment due to its resistance to standard therapies, including surgical resection, radiation, chemotherapy and targeted agents.

Metastatic and relapsed osteosarcoma remains challenging to treat despite the introduction of advanced surgical techniques, intensified chemotherapy and targeted therapies. Adoptive immunotherapies such as CAR T cells, despite being in nascent stages, are considered a potential option for treating aggressive solid tumors such as osteosarcoma.

Researchers from Xi’an Jiaotong University and Southern University of Science and Technology have conducted a comprehensive preclinical study to evaluate the efficacy and safety of a second-generation CAR T therapy targeting trophoblast cell-surface antigen 2 (TROP2) for the treatment of triple-negative breast cancer.

CAR T-cell therapy works by engineering a patient’s T cells to express synthetic receptors that recognize and kill cancer cells without relying on HLA presentation. This approach has shown remarkable success in relapsed or refractory B-cell cancers and multiple myeloma, resulting in several approved treatments. However, no CAR T therapy is currently approved for acute myeloid leukemia (AML) or T-cell acute lymphoblastic leukemia (T-ALL).

Despite the success of traditional viral-based CAR T-cell therapies against several blood malignancies, their efficacy remains limited against solid tumors. Non-viral engineering of CAR T cells using electroporation or lipid nanoparticle delivery of CAR-encoding mRNA achieves high but transient CAR expression, highlighting the limitations of current preclinical models for evaluating mRNA-based CAR T cells.

Hangzhou Qihan Biotech Co. Ltd. has gained IND approval by the FDA for QT-019B, a universal, dual-target CAR T-cell therapy for refractory systemic lupus erythematosus (SLE). A phase I/II trial will be conducted in the U.S.

Orbital Therapeutics Inc. has presented preclinical results supporting the development of OTX-201, a potential best-in-class in vivo CAR T therapy that comprises an optimized circular RNA encoding a CD19-targeted CAR delivered via targeted lipid nanoparticles.

Despite the increasing sophistication of anticancer therapies, many malignancies continue to evade treatment. T cells expressing chimeric antigen receptor (CAR) can effectively attack some tumors by recognizing antigens expressed on the tumor surface, but the therapy may prove ineffective if the target antigen is not abundant enough throughout the tumor.

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.