Frontline therapies for treating colorectal cancer have shortcomings. These include their inability to impede local tumor recurrence and metastatic spread to distant sites such as the abdomen.
Researchers have now utilized a gene therapy approach that simultaneously compromises cancer cell survival while activating immune system cells with cancer-killing abilities.
Gene therapy – an advanced technique developed to insert or inject therapeutic genes into human cells – has shown some success in treating the disease. In a previous study, Xiao and co-investigators at State Key Laboratory of Biotherapy, and the Department of Thoracic Oncology Cancer Center, West China Hospital, Sichuan University, had used a gene therapy approach to induce cancer cell death. Their study found that Vesicular Stomatitis Virus Matrix Protein (VSVMP), when inserted into a cancer cell, compromises the cellular skeletal framework, which is made up of structural proteins. Cell death ensued as a consequence.
In the current study, the research team further armed with VSVMP gene delivery vessel with Interleukin-12 (IL-12) – a protein known to recruit and switch on the cancer-killing functions of immune cells.
The novel drug particles are based on Heparin-polyethyleneimine (HPEI) nanoparticles. To overcome the high toxicity and non-biocompatible nature of PEI, the team used a method to covalently conjugate this substance with heparin.
Their results, based on lab-grown cancer cells and animal studies, suggest that this novel complexed drug molecule (particle size: 53nm) increases tumor cell death, reduces division frequency, and stimulates the recruitment and activation of two types of cancer-killing cells: T cells and NK cells.
Specifically, the drug inhibited the growth of C-26 colon cancer cells. Animal studies showed that the drug reduced tumor weight. Metastatic spread of tumor cells to the abdomen was also reduced. The team proposes that the drug-derived IL-12 induces a secondary cascade of chemical mediators, which in turn recruit and activate cancer-killing immune cells. Their data supports this proposal. Interestingly, their study also found that the complexed drug molecule did not show adverse side effects within the major organs.
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Yuanyuan Xiao, Yuping Yang, Yujiao Wu, Chunmei Wang, Hao Cheng, Wei Zhao, Yang Li, Beibei Liu, Jianlin Long, Wenhao Guo, Guangping Gaoa and Maling Gou