Oncolytic Virotherapy Development for Combination Therapy with Cancer Immunotherapy
Oncolytic viruses represent a new class of drugs for the treatment of cancer. OVs are therapeutics that have been engineered or selected to propagate in and selectively kill cancer cells. As a standalone therapy, the effective of OVs are possibly restricted by the tumor microenvironment, host-mounted anti-viral response as well as pre-existing neutralizing antibodies. Clinical trials have confirmed that combining OVs with conventional anti-cancer therapies can improve the therapeutic responses, such as radiotherapy, chemotherapy, histone deacetylase inhibitors (HDACi) and other forms of immunotherapy. With extensive experience on oncolytic virotherapy and cancer immunotherapy, Creative Biolabs provides one-stop oncolytic virotherapy development for combination cancer immunotherapy of a broad range of project objectives.
In recent years, immunotherapy has been regarded as the "fourth major therapy" after surgery, radiotherapy and chemotherapy in the field of cancer treatment. Cancer immunotherapy mainly includes: adoptive T cell therapy (ACT), immune checkpoint inhibitors (ICI), cytokines, cancer vaccines and biological immunotherapy. Creative Biolabs have developed a comprehensive cancer therapy platform for combining oncolytic virotherapy with cancer immunotherapy specific to various types of disease which are potentially suitable to our clients' demands. As the first-in-class biotech developer and provider, scientists of Creative Biolabs focus on applying outstanding technologies to discover and develop potential therapeutic approaches.
Our combination of cancer therapy services include but not limited to:
Adoptive T cell therapy (ACT) is the process of infusing patients with large numbers of T cells with whole or partial tumor-reactive specificities. OVs can facilitate ACT by conditioning both the systemic immune system and local tumor microenvironment (TME) to better support T cell recruitment and effector function. It was shown that the combination therapy was far more effective than either monotherapy owing to improved T cell effector function.
The following are several therapies:
- Tumor-Infiltrating lymphocyte Therapy (TIL)
- Chimeric Antigen Receptor T-cell Therapy (CAR-T)
- T-cell Receptor-engineered T-cells Therapy (TCR-T)
- Dendritic Cell and Cytokine-Induced Killer Cell Immunotherapy (DC-CIK)
Immune Checkpoint Inhibitors are a relatively new class of immunotherapies that aim to overcome tumor-induced immune suppression and evasion caused by the expression of immune checkpoints.
In particular, cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 (PD1) are two well-studied immune checkpoint molecules. Combination therapies using ICI and oncolytic viruses have significant therapeutic benefit, as the oncolytic virus can recruit TILs into immune-deficient tumors and trigger the release of soluble tumor antigens, danger signals and pro-inflammatory cytokines, which can further increase T cell recruitment and promote immune cell activation.
Cytokine genes (GM-CSF, IL-2, IL-12 and TNF) are a broad and loose category of small proteins which are one of the most commonly introduced immunomodulatory genes, as cytokines recruit and regulate T cell homeostasis. The combination of oncolytic virus and cytokine genes can enhance immune response by promoting APC recruitment and maturation.
Cancer vaccines either treat existing cancers or prevent the development of a cancer. Oncolytic viruses can facilitate the efficacy of cancer vaccines and also can utilize established tumors as an in situ source of neoantigen vaccination through cross-presentation, resulting in regression of distant, uninfected tumors.
Radiotherapy can damage cancer cells and stop them from growing or spreading in the body. The most common types are: external radiotherapy, brachytherapy and radioisotope therapy. It was demonstrated in some studies that the combination of oncolytic virus and radiotherapy has led to increased anti-tumor activity through radiation-mediated enhancement of viral oncolytic and virus-mediated sensitization of cells to radiation therapy.
Chemotherapy uses one or more anti-cancer drugs (chemotherapeutic agents) as part of a standardized chemotherapy regimen. Tumor cells can be killed by chemotherapy, which will release soluble antigens and enhance oncolytic-virus-induced expansion of neoantigen repertoires.
Creative Biolabs has been long devoted to the development and application of oncolytic virotherapy for combination cancer immunotherapy. Based on advanced technologies and years of experience in cancer therapy study, our scientists have developed several cancer therapy platforms to tailor the most appropriate cancer immunotherapy to meet customers' demands. We developed several biomarkers to analyze the temporal course of oncolytic virus infection and their efficacy on tumors, and meanwhile some novel biomarkers are under design, which will play an important role in prospective clinical trials. Furthermore, in order to match different cancer immunotherapies, we also provide services of design, development and transformation of diverse species of oncolytic viruses, as well as both in vitro and in vivo researches. Please feel free to contact us for more details and we are pleased to offer you the best services.
References:
- Chesney, J., Puzanov, I., Collichio, F., Singh, P., Milhem, M. M., Glaspy, J., ... & Logan, T. F. (2018). Randomized, open-label phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma. Journal of Clinical Oncology, 36(17), 1658.
- Ribas, A., Dummer, R., Puzanov, I., VanderWalde, A., Andtbacka, R. H., Michielin, O., ... & Kirkwood, J. M. (2017). Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell, 170(6), 1109-1119.
- Samson, A., Scott, K. J., Taggart, D., West, E. J., Wilson, E., Nuovo, G. J., ... & Kottke, T. J. (2018). Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade. Science translational medicine, 10(422), eaam7577.