Oncolytic Virus Combination Therapies-with Conventional Chemotherapy
Conventional Chemotherapy
Chemotherapy is currently the most effective way to treat cancer. It is called the three major treatments for cancer together with surgery and radiotherapy. Chemotherapy uses chemical drugs to kill tumor cells to achieve the purpose of treating cancer. The treatment principle of chemotherapy is to deliver chemical drugs into the body by injection or oral administration to kill cancerous cells, inhibit the growth and proliferation of cancer cells. Compared with the local treatment of surgery and radiotherapy, chemotherapy is a systemic treatment. Regardless of the route of administration, chemotherapy drugs will be distributed throughout most of the organs and tissues of the body along with blood circulation. Therefore, for some tumors that tend to spread throughout the body and metastatic advanced tumors, chemotherapy is the main treatment. In the treatment of tumors, the application of chemotherapy is becoming more and more extensive. At present, more than ten kinds of tumors such as acute lymphocytic leukemia, testicular seminoma and some malignant lymphomas have been treated by simple chemotherapy in clinical practice, and more than 20 types of tumors can be relieved by chemotherapy. For some tumors that have spread and metastasized, chemotherapy is still the preferred treatment. In addition, the combination of chemotherapy and other therapies can greatly improve the therapeutic effect of malignant tumors and effectively control the spread and metastasis of cancer.
Combination Therapy of Oncolytic Virus with Conventional Chemotherapy
At present, many oncolytic viruses have entered clinical phase III and have shown good or even subversive treatment effects in clinical trials, especially in some cancers with extremely low survival rates such as gliomas. However, the research results also found that the oncolytic virus alone is not effective enough for treatment. Therefore, multiple oncolytic virus drugs are currently undergoing combination therapy, including combining with immunotherapy (e.g. adoptive T cell therapy, immune checkpoint inhibitors), conventional radiotherapy, and chemotherapy. Among them, the combination therapy of chemotherapy and oncolytic virus dominates.
Although immunotherapy has made breakthroughs in cancer treatment in recent years, due to limited efficacy, most drugs are still in the research and development stage, and traditional radiotherapy, chemotherapy and other methods are still at the core. Oncolytic viruses can significantly improve the killing effect of traditional chemotherapy on tumor cells, and at the same time, chemotherapy drugs will not interfere with the replication and cleavage of oncolytic viruses in tumor cells and the expression of therapeutic genes. Therefore, the specially constructed oncolytic virus combined chemotherapy can work with different mechanisms and play a synergistic effect on killing tumors, and the efficacy is better than chemotherapy alone or oncolytic virus therapy alone.
Example
ONYX-015 is an E1B-deficient adenovirus that can replicate in p53-deficient human tumor cells, and has undergone clinical trials for various cancers. In the combined treatment with chemotherapeutic drugs cisplatin and 5-fluorouracil, the study found that the response rate of ONYX-015 to tumors increased from 15% when used alone to 65%. In another clinical trial, the combination of reovirus with BRAF inhibitors and MAPK-ERK kinase (MEK) inhibitors can induce apoptosis through ER stress to enhance tumor cell killing ability. Besides, the results of phase II clinical trial of REOLYSIN combined with paclitaxel treatment also showed that for patients with metastatic breast cancer carrying p53 mutations, this combination therapy can significantly improve the overall survival rate of patients.
At present, a variety of oncolytic viruses and a range of combined drug strategies have entered clinical trials. It is worth noting that when the oncolytic virus is combined with chemotherapy, chemotherapy drugs will also kill immune cells and affect the effectiveness of tumor immunotherapy. In addition, due to the cytotoxicity and pharmacokinetic characteristics of oncolytic viruses, the relationship between chemotherapy and oncolytic viruses has become more complicated.
Creative Biolabs has extensive experience in the development of oncolytic virus therapies and combination therapies. Based on mature oncolytic virus engineering, construction, and in vivo and in vitro verification platforms, we have helped researchers around the world complete their research in developing and evaluating oncolytic virus therapy as well as oncolytic virus combination therapies.