Durable reprogramming of human T cells may now be possible thanks to a new technique based on the CRISPRoff and CRISPRon methodology. Researchers from the Arc Institute, Gladstone Institutes, and the University of California San Francisco (UCSF) have stably silenced or activated genes in this type of immune cell without cutting or altering its DNA, making T cells more resistant, active, and effective against tumors.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, represents about 20% of childhood central nervous system cancers.

Tr1x Inc. has obtained IND clearance from the FDA for TRX-319, paving the way for initiation of a phase I/IIa study in progressive multiple sclerosis (MS) early next year. TRX-319 is designed to combine targeted B-cell control with active anti-inflammatory signaling and T-cell regulation, with the goal of restoring immune balance.

The transition from complex and costly ex vivo strategies to platforms that enable direct cellular intervention within the body, known as in vivo therapies, is marking a paradigm change in the field of gene and cell therapies by simplifying manufacturing, improving tissue targeting and expanding clinical access to treatments.

As the many challenges facing cell therapies are being addressed, the CAR T field continues to evolve beyond its original design of T cells engineered to target hematological malignancies. During the 32nd Annual Congress of the European Society of Gene and Cell Therapy (ESGCT), held in Seville Oct. 7-10, several studies showed how this technology is being redefined as programmable and adaptable immune cells with expanded functional versatility.

Individuals with the inherited disorder Fanconi anemia cannot properly repair damage to their DNA, increasing risk of cancers such as head and neck squamous cell carcinoma (HNSCC).

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.

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.