CAR-T cell therapy has shown effectiveness in treating some individuals with challenging lymphoma. However, for those who experience a relapse, the treatment options become limited. By adjusting the therapy’s molecular target, outcomes have been improved.
Initially, CAR-T cell therapy targeted a specific protein on the surface of cancer cells, leading to tumor shrinkage or disappearance in around 50% of patients with large B-cell lymphoma who did not respond well to chemotherapy treatments.
If this initial CAR-T treatment is not successful, or if the cancer returns, as it does in about half of the cases, the outlook is grim. The average survival period post-relapse is approximately six months.
In a recent phase 1 clinical trial at Stanford Medicine, a new CAR-T cell therapy focusing on a different protein on the cancer cells’ surface demonstrated significantly enhanced outcomes for these patients. Over half of the 38 participants in the trial, including 37 who had previously relapsed from the original CAR-T therapy, achieved a complete response against their cancers. More than 50% of all treated patients survived at least two years after the treatment.
The FDA recently designated this CD22-targeting CAR-T therapy for large B-cell lymphoma as a Breakthrough Therapy in September 2022. This designation aims to accelerate the development and review of promising drugs that could offer substantial improvements over existing treatments for severe conditions.
The study was exclusively conducted at Stanford Medicine, representing an extensive journey from preclinical animal studies to human trials at an academic medical center. The positive preliminary data prompted the FDA to encourage the application for breakthrough therapy designation, streamlining the progress into larger clinical trials.
A phase 2 trial, led by the principal investigator of the phase 1 trial, is currently underway at multiple locations across the country.
CD22, a protein present on mature B cells, has long been considered a potential secondary target for CAR-T cell therapy. Researchers have been exploring dual-targeted CAR-T cell therapies that aim to eliminate cancer cells more effectively before they can evade the treatment.
In this recent trial at Stanford Medicine, immune cells known as T cells were genetically engineered to target CD22 in patients with large B-cell lymphoma who had previously received various therapies, including chemotherapy. The infused T cells led to cancer regression in 68% of the patients, with 53% achieving a complete response where their cancers were undetectable.
The positive outcomes of this trial mark a significant step towards the potential approval of CD22-targeted CAR-T cell therapy for intractable large B-cell lymphoma. The study underscores the integration of medical practice and research, showcasing the ability to adapt and refine approaches swiftly for patient benefit.
While further trials and FDA approval are necessary, the breakthrough designation for this therapy signifies a remarkable achievement and a beacon of hope for patients and their caregivers.
Financial support for the study was provided by various organizations, including the National Institutes of Health, the Virginia and D.K. Ludwig Fund for Cancer Research, and the Parker Institute for Cancer Immunotherapy, among others. Several authors involved in the study have disclosed consulting relationships and research support from pharmaceutical companies in the field.
