PSMA-Targeted CAR-T Therapy for Castration-Resistant Prostate Cancer

 

 

This invention comprises three novel CAR-T therapies which have been genetically engineered to co-express one of three novel PSMA-specific scFvs and a transcription factor as a treatment strategy for castration-resistant prostate cancer. The transcription factor utilized in these CAR-T constructs is a key regulator of effector T cell activity and tissue infiltration. Thus, the co-expression of these two biological components facilitates more selective and potent therapeutic effects. 

 

Stage of Development

 

In vitro data: All 3 PSMA-specific scFvs displayed a high affinity for PSMA in protein and cell based assays. Once the CARs were integrated into the T cells, all 3 of the CAR-T products displayed ~90% cytotoxicity in PSMA expressing cells and no cytotoxicity in non-PSMA expressing cells. 

In vivo data: Anti-cancer activity is currently being assessed in prostate cancer mouse models. 

 

Competitive Landscape

 

There are several reports of PSMA-specific CAR-T therapies which have shown anti-prostate cancer activity, however, majority of these therapies have suffered from immunosuppression and subsequent T cell exhaustion. Studies by the University of Pennsylvania have shown that co-expression of dominant-negative TGFβRII with a PSMA-specific CAR in T cells can successfully prevent these immunosuppressive mechanisms and improve anti-cancer activity. Our invention builds upon this strategy but differs in that it utilizes a novel PSMA CAR and expresses a transcription factor which controls a core regulatory circuit of T cell function. 

 

Competitive Advantages

 

•       Enhanced tissue infiltration

•       Increased cell targeting and killing

•       Reduced off-target affects

•       Synergistic effects with traditional anti-androgen therapy

 

Patent Information:
Licensing Contact
Paige Glumac
pglumac@houstonmethodist.org

Inventors:
Bin He