RESEARCHERS at UCLA have made a groundbreaking advance in cancer immunotherapy by genetically engineering a patient’s blood-forming stem cells to produce a lasting supply of tumor-targeting T cells. This approach transforms stem cells into an in vivo “factory” for cancer-fighting immune cells, potentially overcoming limitations of current therapies, especially against resistant solid tumors.

While conventional CAR-T and T cell receptor (TCR) therapies have succeeded in fighting blood cancers, their effectiveness against solid tumors is limited by T cell exhaustion or short-lived responses.

The UCLA team addressed this challenge by reprogramming hematopoietic stem cells to continuously generate fresh, cancer-specific T cells — effectively creating a self-renewing immune defense.

The clinical trial, published in Nature Communications, represents a first-in-human demonstration of this approach. The study leverages sophisticated gene therapy techniques to genetically modify stem cells with receptors that redirect T cells to recognize cancer-specific markers. Following genetic engineering, these modified stem cells are reintroduced into the patient via a bone marrow transplant, enabling long-term immune surveillance and attack against tumor cells.

The patient cohort consisted of individuals suffering from aggressive sarcomas, where conventional therapies often fall short and relapse rates are notoriously high. In these patients, even after chemotherapy or surgical resection, disease recurrence is common and treatment options remain limited.

Early outcomes from the trial were encouraging. Researchers observed successful engraftment of the engineered stem cells within the patients’ bone marrow, accompanied by the sustained production of cancer-specific T cells detectable for several months post-treatment. In one case, tumor regression occurred, with engineered immune cells persistently attacking the cancer. Imaging and molecular assays confirmed that the reprogrammed stem cells had taken root and were functioning as intended within the host.

Co-author Dr. Antoni Ribas emphasized that this pilot study substantiates the concept that the human immune system can be genetically programmed via stem cells to mount a renewable, cancer-directed response. This realization builds upon prior preclinical work from UCLA and Caltech laboratories, highlighting the translational potential of gene therapy techniques in regenerative immunology.

At present, the approach remains experimental and complex, requiring sophisticated clinical management including stem cell collection, gene editing, conditioning chemotherapy, and careful post-transplant monitoring.

Nevertheless, the UCLA team anticipates that with further development, this therapy could become more accessible and streamlined. Beyond oncology, it can be used to fight chronic viral infections like HIV.(SD-Agencies)