Two independent studies applied CRISPR-based genetic editing – one to treat leukemia and the other to target myeloma – to overcome the challenges faced by CAR T cells, such as exhaustion, impaired activation and fratricide, a phenomenon in which they attack each other.

In cancer, Cdc37 is phosphorylated by casein kinase 2 (CK2) and then the phosphoprotein binds to various kinase ‘clients’ and to the chaperone Hsp90. Hsp90 facilitates the folding of the clients into fully active forms to drive the cell cycle. The plant-derived quinine methid triterpenoid celastrol can inhibit the interaction between Hsp90 and Cdc37 and thereby slow cancer growth by arresting the cell cycle and inducing apoptosis. However, researchers at China Pharmaceutical University China wanted to inhibit the ‘Hsp90-Cdc37-kinase’ cycle at multiple points simultaneously for greater therapeutic effect.

Checkpoint inhibitors have transformed cancer therapy by enhancing immune responses against tumors. However, their effectiveness is limited, as many patients do not respond due to the absence of a pre-existing immunity against the cancer cells. Addressing this gap requires new immunotherapies that can promote cancer-cell antigen recognition and engage multiple immune pathways to effectively reprogram the tumor microenvironment and stimulate a robust antitumor response.

Simcere Zaiming Pharmaceutical Co. Ltd. has obtained IND clearance by the FDA for SIM-0609, a CDH17-targeting antibody-drug conjugate (ADC) for the treatment of advanced solid tumors. An IND was also approved in China earlier this month.

Antibodies that bind to sugars on the surface of cancer cells, rather than to proteins, have not yielded satisfactory results so far due to their low binding affinity. However, scientists at the University of California, Irvine (UCI) have developed therapeutic proteins that recognize so-called tumor-associated carbohydrate antigens (TACAs) using lectins with a robust structure resembling velcro. This design is highly specific and eliminates only tumor cells, regardless of cancer type, while sparing healthy tissues.

Renal cell carcinoma accounts for approximately 90% of kidney cancers, and current treatments fail to prevent metastasis in up to 40% of patients. Potentially effective is immunotherapy based on CAR T cells that recognize CD70, which is little expressed in normal tissues but is expressed in more than 80% of renal cell carcinomas. However, such CAR T immunotherapy has so far not shown overwhelming success against renal cell carcinoma, and the therapeutic cells must be derived for each patient individually.

Boehringer Ingelheim Pharma GmbH & Co KG has advanced a novel T-cell engager resulting from a collaboration with Numab Therapeutics AG into preclinical development for the treatment of lung and gastrointestinal cancers.