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A multifaceted cancer immunotherapy based on an immune checkpoint-modulating chimeric oncolytic virus vector in combination with a dendritic cell vaccine

Project description

Multifaceted oncolytic virus-based approach for cancer immunotherapy

Although immunotherapy has recently emerged as a promising approach to treat cancer, clinical responses, especially in solid tumours, have been disappointing. Hepatocellular carcinoma (HCC) is particularly challenging due to the inherently immune-suppressive microenvironment of the liver. To address this, the EU-funded ONCO-VAX project will use oncolytic viruses (OVs) to directly lyse tumour cells, as an integral part of a multi-faceted dendritic cell vaccine approach to stimulate immune responses against HCC. To overcome potential innate antiviral immune responses, scientists will characterize changes in the tumor microenvironment in response to OV therapy, and use this information to engineer new vectors to express genes that restrict immune suppression. Additional features are expected to elicit a broad and life-long immunity against the tumour.

Objective

Despite many decades of intensive research, cancer remains a major worldwide health concern and imposes a heavy societal burden, both epidemiologically and financially. Cancer immunotherapy is rapidly transforming the face of medical oncology as an exciting paradigm shift in treating cancer by exploiting the immune system of the patient as the basis for the therapy. Although dramatic results have been achieved in a subset of patients, the responses in most solid tumors have been disappointing. Hepatocellular carcinoma (HCC) represents a particularly challenging malignancy to treat, due to the inherently immune-suppressive microenvironment in the liver. Oncolytic viruses (OVs) offer an elegant multimodal approach to combat HCC through their ability to cause direct tumor cell lysis, while stimulating immune responses directed against the tumor. Nevertheless, the potential of OVs as monotherapeutics is limited by the innate antiviral immune response, which rapidly restricts virus replication and spread within the tumor mass. Therefore, a successful therapeutic strategy should employ a combination scheme involving a mechanism to improve the intratumoral dissemination of the OV, while exploiting the immune-stimulatory capacity of the virus, in order to achieve far-reaching synergistic responses that can target metastatic disease. The ONCO-VAX approach aims to accomplish just that. A novel chimeric oncolytic virus backbone with an enhanced cell-cell spreading capacity, will be utilized as a platform to express an optimized gene for eradicating the local immune-suppressive microenvironment in the tumor. As an additional layer of therapy, the virus will be combined with a cutting edge dendritic cell vaccine approach to initiate a broad antitumor response for systemic and potentially life-long immunity against the cancer. This multifaceted approach represents an innovative and crucial step forward in the rapidly evolving field of cancer immuno-oncology.

Host institution

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN
Net EU contribution
€ 1 499 988,00
Address
ISMANINGER STRASSE 22
81675 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 499 988,00

Beneficiaries (1)