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Oncotarget | Systemic oncolytic adenovirus delivered in mesenchymal carrier cells modulate tumor infiltrating immune cells and tumor microenvironment in mice with neuroblastoma


FOR IMMEDIATE RELEASE
2020-02-12

Oncotarget Volume 11, Issue 4: The use of xenografts in immunodeficient mice prevent assessing important clinical aspects of this therapy such as the anti adenovirus immune response or the possible intratumoral immune changes, both of tumor infiltrating leukocytes and of the microenvironment.

However, the presence of circulating anti adenovirus antibodies did not prevent changes detected at the tumor masses: increased infiltration and changes in the quality of immune cells per unit of tumor volume, and a less protumoral and more inflammatory profile of the tumor microenvironment.

In their Oncotarget research article, Dr. Manuel Ramírez & Dr. África González-Murillo from the Unidad de Terapias Avanzadas, Oncología, Hospital Infantil Universitario Niño Jesús, Madrid, Spain, as well as the Fundación de Investigación Biomédica, Hospital Infantil Universitario Niño Jesús, Madrid, Spain and the Instituto de Investigación Sanitaria La Princesa, Madrid, Spain said in their Oncotarget article, "Celyvir (autologous mesenchymal cells -MSCs- that carry an oncolytic adenovirus [1] inside) is a new therapeutic strategy for metastatic tumors developed by our research group over the last decade."

The first clinical trial with Celyvir for children and adults with metastatic and refractory solid tumors and a compassionate use program have shown that Celyvir is a very well tolerated treatment, with only mild toxicities related to the adenoviral infusion with the potential to achieve clinical responses in patients with advanced tumors.

Results of preclinical models and human trials demonstrate that the localized effect of oncolytic viruses is capable of activating an inflammatory immune infiltrate in tumors.

"Results of preclinical models and human trials demonstrate that the localized effect of oncolytic viruses is capable of activating an inflammatory immune infiltrate in tumors."

- Dr. Manuel Ramírez & Dr. África González-Murillo, Unidad de Terapias Avanzadas, Oncología, Hospital Infantil Universitario Niño Jesús

Oncolytic virotherapy, and therefore Celyvir, appears as a strategy capable of achieving tumor infiltration by lymphocytes in any type of tumor, in principle.

In addition to its action on tumor infiltrating leukocytes, oncolytic virotherapy can also act on the tolerant state of the tumor microenvironment.

Figure 1: Kinetic of circulating anti-adenovirus antibodies and viral particles following repeated infusions of mCelyvir. (A) Schematic representation of the experimental procedure. (B) MAV-1 relative quantitation of serum anti-adenovirus antibody levels of mice treated with mCelyvir or naked mAd. (C) qRT-PCR amplification of MAV-1 specific sequence from peripheral blood samples of the same mice.

The use of xenografts in immunodeficient mice allows the analysis of aspects related to oncolysis or tumor targeting but no other important clinical facets such as the anti adenovirus immune response or the possible intratumoral immune changes, both of tumor infiltrating leukocytes and of the microenvironment.

The Ramírez/González-Murillo Research Team concluded in their Oncotarget article that even though these two models are not completely identical, and taking into account differences in the murine and human oncolytic adenoviruses, we believe that the models described here will help us in optimizing this type of therapy by enabling the study of crucial events related to the immune responses affecting both the medicine and the tumor.

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Full text - https://doi.org/10.18632/oncotarget.27401

Correspondence to - Manuel Ramírez - manuel.ramirez@salud.madrid.org África González-Murillo- africa.gonzalez@salud.madrid.org

Keywords - oncolytic virotherapy, neuroblastoma, mesenchymal stem cells, tumor microenvironment, immune response

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