"East Wind Sets Off a Thousand Trees of Flowers Overnight | RocRock Biotech Publishes Milestones in Pan-Cancer Macrophage Drug Development"

TME-Induced Tri-TRAIL Macrophage Vector Demonstrates Exceptional Anti-Tumor Power, Achieving Major Breakthroughs in Cancer Treatment. The company's scientific research team's latest development, a paper titled "Tumor micro-environment induced TRAIL secretion from engineered macrophages for anti-tumor therapy," has been published in the international journal of cellular immunology, Cellular Immunology, with Professor Yin Xiushan, the founder of RocRock Biotech, serving as the corresponding author.

TRAIL, full name Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, has long been considered a highly promising molecule for targeted cancer therapy. However, its limitations in clinical applications have not been properly addressed. To overcome this bottleneck, RocRock Biotech's scientific research team innovatively developed the Tri-TRAIL-iM macrophage vector, an engineered macrophage that activates under specific conditions of the tumor micro-environment (TME) to precisely release trimeric TRAIL (Tri-TRAIL). The design of Tri-TRAIL-iM cleverly utilizes the natural characteristics of macrophages, making them a TME-responsive drug delivery platform. In vitro and in animal models, Tri-TRAIL-iM showed significant cytotoxicity to tumor cells while having minimal impact on normal cells, highlighting its advantages in improving therapeutic efficacy and reducing side effects.

In vitro cellular studies have shown that the conditioned medium of Tri-TRAIL-cM exhibits enhanced cytotoxic activity against tumor cells such as 4T1, B16, and CT26 to varying degrees. This finding confirms the high efficiency of Tri-TRAIL in promoting apoptosis in tumor cells, especially in co-culture experiments, where its apoptotic induction effect on 4T1 cells is more pronounced.

Furthermore, the team utilized the Arg1 promoter to engineer Tri-TRAIL-iM, which exhibits low levels of TRAIL secretion under normal culture conditions. However, upon induction with tumor-conditioned medium (T-CM), the levels of TRAIL significantly increase, demonstrating a specific response to the tumor microenvironment (TME). Under TME stimulation, Tri-TRAIL-iM not only activates the transcription of pro-inflammatory genes but also avoids non-specific cytotoxicity, thereby enhancing its anti-tumor efficacy. This innovative strategy provides a new approach to improving the precision of cancer treatment and reducing side effects.

Researchers established a subcutaneous tumor model in mice using 4T1 cells and assessed the expression of Tri-TRAIL-iM in tumor and normal tissues through immunostaining. The experimental results showed that Tri-TRAIL-iM induced a high level of TRAIL expression in tumor tissues, comparable to the Mono-TRAIL-cM group. However, unlike Mono-TRAIL-cM, which also exhibited TRAIL expression in several normal organs, no accumulation of TRAIL was observed in non-tumor tissues with Tri-TRAIL-iM, demonstrating its excellent tumor specificity and potential to reduce side effects on non-tumor tissues.