Good news! Cancer is history (soon)!
"Key takeaways:
- UCLA researchers have developed a new type of immunotherapy called CAR-NKT cell therapy that, in patient-derived tumor samples, has been shown to be more effective at fighting ovarian cancer than conventional CAR-T cell therapy.
- Unlike current cellular immunotherapies that require patient-specific manufacturing and can cost hundreds of thousands of dollars, CAR-NKT cells can be produced off-the-shelf, lowering costs to approximately $5,000 per dose.
- The CAR-NKT platform shows promise for treating lung, brain and other solid tumors that have been challenging for CAR-T cell therapies to tackle.
..."
From the extended abstract:
"Context and significance
Ovarian cancer remains one of the most lethal gynecologic malignancies, often recurring due to treatment resistance and immune evasion.
Current chimeric antigen receptor-engineered T (CAR-T) cell therapies have shown limited success against ovarian cancer, largely due to tumor heterogeneity and an immunosuppressive tumor environment.
This study explores an alternative approach using allogeneic CAR-engineered invariant natural killer T (AlloCAR-NKT) cells derived from blood stem cells. By applying a clinically guided culture method, the researchers generated AlloCAR-NKT cells with high efficiency, purity, and potent antitumor activity. These engineered cells not only directly target tumor cells but also remodel the tumor environment and display a favorable safety profile. The findings suggest that AlloCAR-NKT cells offer a safer, more effective, and readily available immunotherapy for patients with ovarian cancer.
Highlights
• AlloCAR-NKT cells overcome OC resistance and evasion hindering CAR-T cells
• AlloCAR-NKT cells exhibit potent efficacy with tumor homing and TME modulation
• AlloCAR-NKT cells minimize cytokine release syndrome toxicity
• AlloCAR-NKT cells induce minimal GvHD and resist host cell-mediated allorejection
Summary
Background
Ovarian cancer (OC) poses a significant challenge for conventional chimeric antigen receptor-engineered T (CAR-T) cell therapy, due to frequent recurrence linked to tumor heterogeneity, platinum resistance, immune evasion, and an immunosuppressive tumor microenvironment (TME).
Methods
Here, we analyze primary OC patient samples and identify a unique opportunity for allogeneic CAR-NKT (AlloCAR-NKT) cells to concurrently attack OC tumor cells and their TME. Leveraging stem cell gene engineering and a clinically guided culture method, we achieve robust generation of AlloCAR-NKT cells at high yield and purity.
Findings
Compared to conventional CAR-T cells, AlloCAR-NKT cells demonstrate superior anti-OC efficacy, showcasing multiple OC-targeting mechanisms, focused tumor homing, and pronounced TME modulation.
AlloCAR-NKT cells also exhibit a high safety profile with reduced cytokine release syndrome.
Additionally, these cells do not induce graft-versus-host disease and resist host immune-cell-mediated allorejection.
Conclusions
These findings underscore the unique efficacy and safety advantages, as well as the off-the-shelf potential of AlloCAR-NKT cell therapy for OC."
Figure 1 Transcriptome and biomarker profiling of primary OC tumor cells and their TME identifies opportunities for CAR-NKT cell therapy
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