Research on OV Immunotherapy

A Short Explanation

Oncolytic viruses (OV) are viruses, generally injected directly into cancerous tumors, that destroy cancer cells while doing little or no damage to normal cells in the human body. For example, the Newcastle disease virus (NDV) has been shown to selectively infect cancer cells and rapidly replicate in them. The virus induces an immune response which then fights the tumor. The overall side effects of such a virus in humans are mild. Below we present research articles that delve into the details of oncolytic virus therapy.

Dr. Beni Gesundheit, MD PhD​

Dr. Beni Gesundheit is Rapo Yerape BH Ltd.’s CEO and Chief Medical Officer.  He has been researching the therapeutic effects of oncolytic viruses since 2015. 

Dr. Gesundheit has clinical and research experience in oncology.  His past experience includes working in the departments of Pediatric Hematology-Oncology at the Hospital for Sick Children in Toronto, Canada; the departments of Pediatric Hematology-Oncology at Soroka Hospital, Beer Sheva, Israel and at Hadassah Hospital, Jerusalem, Israel. He was awarded an MD from the University of Basel, Switzerland (1992) and a PhD in Bioethics from University of Toronto, Toronto (2004). He has published peer reviewed  articles in oncology including oncolytic viruses.

To further the mission of the ATGesundheit Institute, Dr. Gesundheit and his team carry out observational studies of cancer patients undergoing investigational treatment relating to Oncolytic Virus & Cancer Immunotherapy and also review patient medical histories to enhance their health and safety. Patients with late-stage and/or metastatic cancers may submit their medical data for review and evaluation by the ATGesundheit Institute.

Specific OVT Cancer Research

Research articles with bold headings were written or edited by members of

Glioblastoma multiforme (GBM) remains an incurable condition, associated with a median survival time of 15 months with best standard of care and 5-year survival rate of <10%. We report on four GBM patients on combination treatment regimens that included oncolytic virus (OV) immunotherapy, who achieved clinical and radiological responses with long-term survival, thus far, of up to 14 years, and good quality of life. We discuss the radiological findings that provide new insights into this treatment, the scientific rationale of this innovative and promising therapy, and considerations for future research.  Read more Authors: Benjamin Gesundheit, Eliel Ben-David, Yehudit Posen, Ronald Ellis, Guido Wollmann, E. Marion Schneider, Karl Aigner, Lars Brauns, Thomas Nesselhut, Ingrid Ackva, Christine Weisslein and Arno Thaller Publication: Frontiers in Oncology

The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. A dose-finding and toxicity study was conducted in this population of patients, evaluating convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment. Read more

Authors: ​Annick Desjardins, M.D., Matthias Gromeier, M.D., James E. Herndon, II, Ph.D., et al.

Publication: New England Journal of Medicine

A presentation on GBM – treatments, challenges & outcome. Including new strategies with OV, DC, CPI, a presentation on 4 Patients and a discussion of the new GBM protocol. Read More

Author: Benjamin Gesundheit, MD. PhD

Presented at:  V Konferencja Immunoterapia Nowotworow, 2019

A 40-year-old, Caucasian patient with a grade-3 estrogen receptor-, progesterone receptor-, Her2-positive breast tumor and two lung nodules was treated with intramuscular targeted immunotherapy with trastuzumab and oral tamoxifen hormone therapy, together with customized intra-tumoral oncolytic virotherapy (IT-OV) over a 17-month period. PET/CT imaging at 3 and 6 months showed increased primary tumor size and metabolic glucose uptake in the primary tumor, axillary lymph nodes and lung nodules, which were paralleled by a hyperimmune reaction in the bones, liver, and spleen. Thereafter, there was a steady decline in both tumor size and metabolic activity until no radiographic evidence of disease was observed. The treatment regimen was well tolerated and good quality of life was maintained throughout. Read more

Authors: Benjamin Gesundheit, Alexander Muckenhuber, Yehudit Posen, Ronald Ellis, Philip David Zisman, Harald Schmoll, Christine Weisslein and Jayadeepa Srinivas Raju

Publication: Frontiers in Oncology

Viruses team up with cancer immunotherapy

Immune checkpoint inhibitors have shown great promise for cancer therapy, but they do not treat all cancers, and neither breast nor brain tumors are usually treatable with these drugs. However, Bourgeois-Daigneault et al. discovered a way to address this for breast cancer, and Samson et al. discovered a way to address this for brain tumors. In both cases, the authors found that oncolytic virus treatment given early, before surgical resection, alters the antitumor immune response and potentiates the effects of subsequent treatment with immune checkpoint inhibitors. Read more

Authors: Marie-Claude Bourgeois-Daigneault, Dominic Guy Roy, Amelia Sadie Aitken, et al.

Publication: Science Translational Medicine

Breast cancer continues to be a leading cause of mortality among women. While at an early stage, localized breast cancer is easily treated; however, advanced stages of disease continue to carry a high mortality rate. The discrepancy in treatment success highlights that current treatments are insufficient to treat advanced-stage breast cancer. Read more

O Bryan SM, Mathis JM

Publication:  Current Gene Therapy

A palliative patient with a refractory end-stage metastatic gastroesophageal tumor did not respond to
conventional chemotherapy, lost the ability to swallow, and was considered palliative. She then was
treated with Locoregional Chemotherapy (LRC), followed by oncolytic virus immunotherapy with
intratumor injection of three Oncolytic Viruses (OV). Read more

Authors: Benjamin Gesundheit, Jayadeepa Srinivas Raju, Yehudit Posen, Ronald Ellis, Karl Aigner
and Arno Thaller

Publication: Oncology Case Reports Journal

Oncolytic viruses (OV) represent a novel, mechanistically distinct therapy with significant anti-tumor potential and minimal toxicity. Crucial to OV efficacy is their induction of immunogenic cell death resulting in tumor associated antigen (TAA) uptake by dendritic cells (DCs) and cross-presentation to TAA-reactive T cells.  Read more

Authors: Judit Svensson-ArvelundSara Cuadrado-Castano, et al.

Publication: The Journal of Immunology

Melanoma often spreads to cutaneous or subcutaneous sites that are amenable to direct, intralesional injection. As such, developing effective injectable agents has been of considerable interest. Talimogene laherperepvec (T-VEC) is an injectable modified oncolytic herpes virus being developed for the treatment of advanced melanoma. Read more

Authors: Douglas B Johnson, Igor Puzanov, and Mark C Kelley

Publication: Immunotherapy

General OVT Research

For more than a century, doctors have been interested in using viruses to treat cancer, and in recent years a small but growing number of patients have begun to benefit from this approach.

Some viruses tend to infect and kill tumor cells. Known as oncolytic viruses, this group includes viruses found in nature as well as viruses modified in the laboratory to reproduce efficiently in cancer cells without harming healthy cells. Read more

Authors: NCI Staff

Publication:  The National Cancer Institutes 

Oncolytic viruses (OVs) are a versatile new class of therapeutic agents based on native or genetically modified viruses that selectively replicate in tumor cells and can express therapeutic transgenes designed to target cells within the tumor microenvironment and/or host immunity. Read more

Authors: Praveen K. Bommareddy and Howard L. Kaufman

Publication: The Journal of Clinical Investigation

OVs often induce immunogenic cell death (ICD) of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. The authors of this study and others have developed a number of strategies
to further stimulate antitumor immunity and to productively modulate the tumor microenvironment
(TME) for potent and sustained antitumor immune cell activity. Read more

Authors: Zong Sheng Guo1, Zuqiang Liu1, Stacy Kowalsky1, et al

Publication:  Frontiers in Immunology

Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses.  Read more

Authors: Raja, J., Ludwig, J.M., Gettinger, S.N. et al.

Publication: Journal for ImmunoTherapy of Cancercat

Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. Read more

Authors: Hiroshi Fukuhara, Yasushi Ino, and Tomoki Todo

Publication:  Cancer Science

With the recent success of oncolytic viruses in clinical trials, efforts toward improved monitoring of the viruses and their mechanism have intensified. Four main gene expression strategies have been employed to date including: analyzing overall gene expression in tumor cells, looking at gene expression of a few specific genes in the tumor cells, focusing on gene expression of specific transgenes introduced into the virus, and following gene expression of certain viral genes.  Read more

Authors: Ashley Ansel, Joshua P. Rosenzweig, Philip D. Zisman, Beni Gesundheit

Publication: Frontiers in Oncology

The ability to genetically engineer oncolytic viruses in order to minimize side effects and improve the selective targeting of tumor cells has opened up novel opportunities for treating cancer. Understanding the mechanisms involved and the complex interaction between the viruses and the immune system will undoubtedly help guide the development of new strategies. Theranostic biomarkers to monitor these therapies in clinical trials serve an important need in this innovative field and demand further research.  Read more

Editors: Benjamin Gesundheit and Joshua P. Rosenzweig
Publication: Frontiers in Oncology and Frontiers in Immunology

Localized oncolytic virotherapy overcomes systemic tumor
resistance to immune checkpoint blockade immunotherapy

Preexisting lymphocytic infiltration of tumors is associated with superior prognostic outcomes in a
variety of cancers. Recent studies also suggest that lymphocytic responses may identify patients
more likely to benefit from therapies targeting immune checkpoints, suggesting that therapeutic
efficacy of immune checkpoint blockade can be enhanced through strategies that induce tumor
inflammation. Read more

Authors: Dmitriy Zamarin, Rikke B. Holmgaard, Sumit K. Subudhi et al.

Publication: Science Translational Medicine

About us

The ATGesundheit Institute website presents information about oncolytic virus (OV) cancer immunotherapy for glioblastoma multiforme (GBM), solid tumors and breast cancer. Our website is dedicated to exploring the therapeutic potential of OVs for incurable tumors and the therapeutic mechanisms of various OVs.

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