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Currently, immunotherapy is effective only in 15% - 30% of cancer patients

  • A new therapeutic strategy consisting of the administration of oncolytic viruses inside the primary tumor and / or metastases could increase the efficacy of intravenous immunotherapy and reduce its adverse effects

  • This strategy seems to be especially effective in aggressive and rapidly growing tumors, so pancreatic tumors, brain tumors or triple negative breast cancer in particular could benefit from this new therapy

Administration by direct injection into the initial tumor or metastases of oncolytic virus may increase the efficacy of immunotherapeutic treatments (currently, they are effective in only 15%-30% of patients) and, therefore, increase survival of cancer patients. In addition, the first studies on this innovative therapeutic strategy seem to indicate that the technique may be more effective, the more aggressive and rapidly growing the tumor, which points to brain tumors and triple negative breast cancer - two of the tumors with lower life expectancy today, as possible candidates for this novel therapeutic strategy.

At the same time, administration of this therapy directly into the tumor may reduce the characteristic side effects of immunotherapy and even delay the onset of resistance to treatment. As Dr. Enrique Grande, head of the Medical Oncology Service at MD Anderson Cancer Center Madrid, explains, "these results open the door to a totally different way of treating tumors, trying to increase the products of the tumor that are released and that are, therefore, more susceptible to being recognized by the patient's own immune system (neoantigens) reacting to them in the same way that it responds to bacteria".


First results in preclinical phases

The journal 'Science' has published in its January issue two studies demonstrating the increased efficacy of immunotherapeutic drugs in mouse models thanks to the prior administration of oncolytic viruses. Specifically, an article by Canadian scientists has shown that injecting these viruses into the primary triple-negative breast tumor of a mouse model increases the subsequent efficacy of immunotherapeutic drugs administered intravenously. A second article published by British authors, also in January, in the journal 'Science' has shown a similar hypothesis in murine models with brain tumors.

In addition to these two studies in triple negative breast cancer and brain cancer, there are currently ongoing clinical trials in phases 1 and 2 in lymphoma or pancreatic cancer and even a phase 3 trial in melanoma.

But why can injecting a virus inside the tumor increase the effectiveness of immunotherapeutic drugs? As Dr. Grande explains, "Once genetically modified viruses are administered directly into the tumor, they infect the tumor cells and destroy them locally." This destruction causes the release of tumor antigens and therefore facilitates their recognition by the immune system. Thanks to the greater exposure to the tumor's own antigens, the immune system will be able to recognize the cells that carry these tumor antigens more easily and, therefore, will be more effective in destroying them.

Thus, Dr. Grande emphasizes, "It is confirmed that it is possible to increase the stimulation of the immune system to achieve greater effectiveness of immunotherapeutic drugs and, in addition, a reduction in adverse effects." And precisely one of the main advantages of this therapeutic strategy is that "with more local and specific stimulation, the adverse effects and toxicities of immunotherapy are limited". And furthermore, the technique of selective inoculation on the different metastatic lesions present in the patient may also prevent tumor heterogeneity, currently the main route of resistance to immunotherapy and targeted therapies.


Pending challenges

Although promising, the potential of this technique still has many unresolved questions that Dr. Grande hopes further research in this field will be find answers to. Thus, for example, the specialist points out that "this therapy would be like a vaccine, which makes us wonder whether one dose will be enough to sensitize the immune system or revaccinate."

Also, it is still early days to know whether the administration of several treatments with immunotherapy, radiotherapy or chemotherapy in combination with this viro-therapy will be viable, or what will be the best time to evaluate of the response to treatment. Many questions remain for a very promising therapy that aspires to change the paradigm of the treatment of a disease that will affect two out of three men and one in three women throughout their life.