Bluebird bio has shown cancer gene therapy vectors boost the efficacy of its CAR-T therapy in mice. The study assessed the effect of giving bluebird’s anti-EGFR CAR-T cells in combination with vectors in development at PsiOxus Therapeutics.
PsiOxus and bluebird began exploring the combination in light of the limitations of monotherapies in solid tumors. CAR-T cells have underwhelmed so far in solid tumors, potentially because the tumor microenvironment stops them from infiltrating the cancer and killing its cells. It may be necessary to tackle the immunosuppressive environment to make CAR-T cells effective in solid tumors.
The bluebird-PsiOxus work assessed the ability of cancer gene therapy vectors based on the oncolytic adenovirus enadenotucirev to make the microenvironment more hospitable to T cells. The vectors encoded for immunomodulatory molecules to encourage T-cell recruitment and activation.
In mice implanted with human lung cancer A549 xenografts, neither the anti-EGFR CAR-T cells nor the cancer gene therapy vectors showed efficacy or delayed disease progression when administered as a single agent. However, in combination, the drug candidates cleared the xenograft and pulmonary metastases. Expression of the virus-encoded transgenes was evident.
“These data validate the potential of our T-SIGn platform to reprogram the tumor microenvironment such that CAR-T cells are recruited, activated and sustained within solid tumors to yield efficacy,” John Beadle, CEO of PsiOxus, said in a statement. Buoyed by the findings, PsiOxus plans to continue evaluating its T-SIGn vectors in combination with T-cell therapeutics in solid tumors.
PsiOxus is already testing one of its vector programs, NG-641, in humans. A first-in-human study in patients with metastatic or advanced epithelial tumors began last year, and a checkpoint inhibitor combination trial is in the works. Another vector program, NG-347, is at the IND-enabling stage.