It coincides with the time that the 14th Geriatric Oncology Conference-Oncolytic Virus Therapy Symposium was grandly held

Oncolytic virus is an important tumor biological immunotherapy, and it is also one of the current research hotspots of tumor immunotherapy
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On July 17, 2021, the 14th Geriatric Oncology Conference-Oncolytic Virus Therapy Symposium opened in the cloud.
The experts at the conference shared and interpreted the latest research progress and key clinical data of oncolytic viruses, bringing an academic feast
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Professor Xiao Shaowen from Peking University Cancer Hospital and Professor Zhang Yuewei from Beijing Tsinghua Chang Gung Memorial Hospital served as the chairpersons.
Professor Jiang Jing from Beijing Tsinghua Chang Gung Memorial Hospital and Professor Deng Lei from Cancer Hospital of Chinese Academy of Medical Sciences delivered wonderful speeches
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Professor Jiang Jing: The latest research progress of oncolytic viruses.
Oncolytic viruses are a class of natural or recombinant viruses that can selectively infect and kill tumor cells without damaging normal cells
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Since the State Food and Drug Administration (CFDA) approved the first oncolytic virus drug recombinant human adenovirus type 5 (H101) combined with chemotherapy for the treatment of patients with advanced nasopharyngeal carcinoma in 2005, the number of oncolytic virus studies has been increasing.

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Up to now, there have been more than 100 oncolytic virus-related clinical studies registered on ClinicalTrials worldwide
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In 2015, the U.
S.
Food and Drug Administration (FDA) and the European Medicines Agency successively approved type I herpes simplex virus T-VEC to treat advanced melanoma, which further promoted the development and maturity of oncolytic virus therapy
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Oncolytic viruses are becoming one of the important methods of cancer immunotherapy
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Professor Jiang Jing introduced that oncolytic viruses exert their anti-tumor effects through four modes of action: oncolysis, anti-tumor immunity, anti-angiogenesis, and genetic modification to enhance oncolysis.

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Targeting cancer stem cells may be a new direction for oncolytic virus research
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In addition, oncolytic viruses have a synergistic effect with different immunotherapies
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 Four modes of action of oncolytic virus therapy There will be one and three Chinese oncolytic virus studies announced at the 2020 and 2021 American Society of Clinical Oncology (ASCO) annual meetings.
Professor Jing Jiang said that this indicates that Chinese oncolytic viruses are used in entities.
There are more and more studies on tumors, and most studies have proved that oncolytic viruses have better efficacy and safety, and they have also proved to be more effective in combination with immune checkpoint inhibitors
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 The latest progress of oncolytic viruses on ASCO.
Among them, the results of a phase I clinical study of H101 combined with standard therapies for the treatment of liver metastases from colorectal cancer led by Professor Xu Qing from Shanghai Tenth People’s Hospital showed that no dose limitation was observed in terms of safety.
Toxicity (DLT) and adverse events (AE)> grade 4, the main AEs are fatigue, fever, chills, abdominal pain and night sweats
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In terms of efficacy, among the 8 patients, 1 had partial remission (PR), 6 had stable disease (SD), and 1 had progressed disease (PD).
Among the 8 patients, 6 had a tumor marker CEA reduction
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The study showed that H101 combined with standard therapies for the treatment of colorectal cancer liver metastasis is safe and has a certain initial effect
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Combination therapy is an important means to improve the efficacy of anti-tumor.
Oncolytic virus combined chemotherapy, radiotherapy, targeted therapy and immunotherapy are being studied in full swing
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Professor Jiang Jing finally concluded that the oncolytic virus was re-edited to optimize the anti-tumor efficacy and improve the safety
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The preclinical and clinical evidences of oncolytic virus treatment of tumors are abundant, and the development prospects are broad
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At the same time, oncolytic virus therapy inevitably faces some challenges and requires deeper research
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Professor Deng Lei: Interpretation of the key data on oncolytic viruses (listed) Currently, most clinical studies on oncolytic viruses are in the phase I clinical research stage.
Professor Deng Lei mainly introduced two types of oncolytic viruses that have completed phase III clinical studies and have been approved for marketing.
Oncovirus drugs: T-VEC and H101
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T-VECT-VEC is a genetically modified herpes simplex virus type 1 (HSV-1), the first oncolytic virus drug approved by the FDA
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It can replicate and express the immune activating protein granulocyte-macrophage colony stimulating factor (GM-CSF) in tumor cells, accelerate the anti-tumor immune response, and is mainly used for the treatment of advanced melanoma
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The T-VEC-related clinical study OPTiM study is the first phase III randomized controlled study to evaluate the efficacy of oncolytic virus therapy in patients with advanced melanoma
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The results showed that the long-term effective rate, objective remission rate (ORR) and complete remission (CR) rate of T-VEC in the treatment of advanced melanoma were significantly improved
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In addition, compared with GM-CSF, T-VEC significantly prolongs the overall survival (OS) of melanoma patients
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T-VEC is the first new oncolytic virus therapy to prove clinical benefit for melanoma in a phase III clinical trial
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A phase Ib clinical study of T-VEC combined with PD-1 inhibitors in the treatment of melanoma showed that there was no DLT in the combination, and the ORR reached 62%, of which the CR rate was 33%, and the effect was significant
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Further analysis revealed that T-VEC combined with PD-1 inhibitors promoted T cell infiltration in tumors.
T-VEC can increase tumor tumor infiltrating lymphocyte density and PD-L1 expression, which is also the possible reason for the improved efficacy of combined therapy One
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H101H101 is the world's first and only oncolytic virus anti-tumor drug marketed in China
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Professor Deng Lei introduced that H101 is an oncolytic adenovirus recovered after deleting part of human type 5 adenovirus E1B-55KD and E3 gene fragments using genetic engineering technology.
It can replicate specifically in tumors with p53 gene deficiency or abnormality.
It also produces replication-dependent cytotoxicity, but has no obvious cytotoxic effect on normal human cells.
It has a unique dual mechanism-precise oncolysis and systemic immunity
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Good safety, low harm to the environment and operators.
In the phase I safety study, PCR detection of blood, urine, injection site, and throat swab was carried out.
No H101 virus was detected within the detection sensitivity range, and no H101 was found after administration.
Spread to the body, there is no evidence that it has obvious environmental hazards
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A summary analysis of adverse reaction data from phase I-III registered clinical studies showed that the adverse reactions of H101 were mostly mild, indicating that its safety is good
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It is effective for a variety of solid tumors, and the combined treatment effect is better.
1) A phase II clinical trial showed that the ORR of H101 monotherapy for 13 kinds of advanced malignant tumors was 22.
4%, and the ORR of combined chemotherapy was increased by 17.
4% compared with chemotherapy alone
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2) A phase III clinical study showed that H101 combined with chemotherapy compared with chemotherapy alone in the treatment of patients with squamous cell carcinoma of the head and neck and esophagus, the ORR increased by 32.
3%, and the ORR of the first-line treatment increased by 39.
2%
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3) A retrospective study evaluated the clinical benefit of H101 combined with transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC)
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The results showed that compared with TACE alone, the ORR of H101 combined with TACE increased by 24.
5%, and the median OS was extended by 1.
2 months
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4) H101 has a clear infection and inhibitory effect on lung cancer cells
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An animal experiment showed that H101 can inhibit the cell viability of lung cancer cells after infection, proving that H101 can inhibit the growth of lung cancer xenografts in vivo
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H101-related clinical research currently underway in China Finally, Professor Deng Lei concluded that oncolytic virus therapy is a new generation of biological immunotherapy with multiple advantages
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The multiple anti-tumor mechanisms of oncolytic viruses make it effective against multiple solid tumors and have high safety.
Combination of chemotherapy, radiotherapy, targeted therapy or immunotherapy can significantly enhance the anti-tumor efficacy and is a kind of anti-tumor therapy with great potential
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At the end of the conference, Professor Shaowen Xiao and Professor Yuewei Zhang expressed their gratitude to the two experts for their wonderful sharing, and expressed their expectation that oncolytic virus research can make more progress and breakthroughs, and continue to shine in the immunotherapy era
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