Good news! Cancer is history (soon)!
"Key takeaways
- ... researchers have developed a CAR-NKT cell therapy that has shown to be more effective than current immunotherapies at fighting cancer in tumor samples from late-stage triple-negative breast cancer patients.
- While personalized treatments can cost six figures and require weeks to manufacture, this therapy can be mass-produced from donated blood stem cells and stored ready-to-use at about $5,000 per dose.
- The same cell product could potentially be used to treat multiple solid tumors like ovarian, pancreatic and lung cancers — all of which express the protein mesothelin.
...
researchers have developed a novel therapy that could fundamentally change the treatment plan for this deadly disease. In a study ..., the team details how this new type of immunotherapy, called CAR-NKT cell therapy, could attack tumors from multiple fronts while dismantling their protective shields. ...
The therapy uses engineered immune cells called CAR-NKT cells, which can be mass-produced from donated blood stem cells and stored ready-to-use. This off-the-shelf approach offers an immediately available treatment option at a fraction of the cost of current personalized cell therapies, which can soar into the hundreds of thousands of dollars. ...
To tackle these hurdles, the ... team’s cell therapy harnesses a rare but powerful type of immune cell called invariant natural killer T cell, or NKT cell. When equipped with a chimeric antigen receptor, or CAR, targeting mesothelin — a protein found on triple-negative breast cancer cells — these potent tumor-fighting cells gain the ability to recognize and destroy cancer through three distinct mechanisms.
The first mechanism uses the engineered CAR to target mesothelin, which is associated with more aggressive, metastatic disease.
The second leverages the cells’ natural killer receptors that recognize more than 20 molecular markers, making it nearly impossible for tumors to evade all of them.
The third employs the cells’ unique T cell receptor to reshape the tumor microenvironment by eliminating immunosuppressive cells. ..."
From the abstract:
"Background
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the lack of ER, PR, and HER2 expression. Its aggressive behavior, high degree of tumor heterogeneity, and immunosuppressive tumor microenvironment (TME) are associated with poor clinical outcomes, rapid disease progression, and limited therapeutic options. Although chimeric antigen receptor (CAR)-engineered T cell therapy has shown certain promise, its applicability in TNBC is hindered by antigen escape, TME-mediated suppression, and the logistical constraints of autologous cell production.
Methods
In this study, we employed hematopoietic stem and progenitor cell (HSPC) gene engineering and a feeder-free HSPC differentiation culture to generate allogeneic IL-15-enhanced, mesothelin-specific CAR-engineered invariant natural killer T (Allo15MCAR-NKT) cells.
Results
These cells demonstrated robust and multifaceted antitumor activity against TNBC, mediated by CAR- and NK receptor-dependent cytotoxicity, as well as selective targeting of CD1d+ TME immunosuppressive cells through their TCR. In both orthotopic and metastatic TNBC xenograft models, Allo15MCAR-NKT cells demonstrated potent antitumor activity, associated with robust effector and cytotoxic phenotypes, low exhaustion, and a favorable safety profile without inducing graft-versus-host disease.
Conclusions
Together, these results support Allo15MCAR-NKT cells as a next-generation, off-the-shelf immunotherapy with strong therapeutic potential for TNBC, particularly in the context of metastasis, immune evasion, and treatment resistance."
Fig. 1 Primary metastatic TNBC patient sample profiling highlights the therapeutic potential of CAR-NKT cells.
Fig. 2 Allogeneic stem cell-derived MCAR-NKT cells are generated using a clinically guided culture method and display prominent NK-like features and potent cytotoxic activity.
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