On April 14, 2021 PsiOxus Therapeutics, Ltd. (PsiOxus), a clinical stage oncology company ​re-programming ​the tumor microenvironment to overcome the central challenge of resistance to therapy, and bluebird bio, Inc. (Nasdaq: BLUE) reported that preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (Press release, bluebird bio, APR 14, 2021, View Source [SID1234578016]). The study, "T-SIGn cancer gene therapy and anti-EGFR CAR-T cells synergize in combination therapy to clear A549 lung tumor xenografts", assessed anti-tumor synergy between PsiOxus’ T-SIGn vectors and an anti-epidermal growth factor receptor (EGFR) chimeric antigen receptor (CAR)-T cell therapy from bluebird bio in xenograft lung tumors.

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"We are encouraged by these results showing synergistic activity between our T-SIGn vector and bluebird bio’s CAR-T therapy in primary and metastatic solid tumors and are particularly excited by the ability of a single IV cycle of T-SIGn to enable an otherwise non-effective dose of CAR-T cells to clear both primary and metastatic tumors," said John Beadle, M.D., Chief Executive Officer, PsiOxus. "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. We look forward to further evaluating our T-SIGn vector programs in combination with T-cell therapeutics that otherwise fail to meet their true potential to treat solid cancers."

"Cracking the solid tumor code will likely require layers of technology to reach the types of deep and durable response we aspire to as a field," said Philip Gregory, chief scientific officer, bluebird bio. "This collaboration between bluebird and PsiOxus is an example of this layered strategy, combining the power of two orthogonal anti-tumor approaches to achieve a synergistic impact on tumor control and clearance."

"Although it’s early in development, we believe that this is one of the most robust data sets so far showing that an IV administered therapy is able to rewire the tumor microenvironment to enable recruitment and activation of CAR-T cells and expand the efficacy of CAR-T therapies to solid tumors, including metastases," said Brian Champion, Ph.D., Chief Scientific Officer, PsiOxus. "Results of this study validate the mechanistic foundation of our T-SIGn platform and provide a blueprint of what can be achieved as we evaluate our T-SIGn vectors in combination with additional cell therapy approaches."

The study showed that when injected intravenously into mice with established human tumor xenografts, PsiOxus’ armed T-SIGn vectors reprogrammed the tumor microenvironment to a proinflammatory state. When this was followed three days later by a dose of bluebird bio’s anti-EGFR CAR-T cells, two T-SIGn vectors armed with different T-cell recruitment and activation transgenes, NG-347 and NG-641, synergistically yielded anti-tumor activity. The anti-EGFR CAR-T cells demonstrated no tumor efficacy when dosed alone at the same dose and also failed to synergize with the unarmed T-SIGn vector, demonstrating that the synergy was driven by the T-SIGn vectored transgene expression within the tumor. Transcriptional analysis showed that PsiOxus’ NG-347 T-SIGn vector reprogrammed the tumor microenvironment leading to enhanced activation of CAR-T cells through robust CAR-T and innate immune cell recruitment and activation, resulting in increased efficacy against both primary and metastatic tumors.

While NG-347 is a preclinical program in the IND enabling phase, NG-641 is already being evaluated in the clinic and PsiOxus plans to develop it both as a monotherapy and in combination with checkpoint inhibitors.

"This preclinical data opens up an additional valuable combination option for NG-641 to enable the effective treatment of a wide range of solid tumors with CAR-T or other cell therapies," concluded Brian Champion, Ph.D., Chief Scientific Officer, PsiOxus.

The poster, "T-SIGn cancer gene therapy and anti-EGFR CAR-T cells synergize in combination therapy to clear A549 lung tumor xenografts", is available to registered participants of the AACR (Free AACR Whitepaper) Virtual Annual Meeting 2021 and can be downloaded from the PsiOxus website.