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Oncolytic virus combined with PD-1/L1 antibody, the best partner or a magic weapon to break the bottleneck!

 Last Update: 2022-11-15
 Source: Internet
 Author: User

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Immuno-oncology has attracted much attention
due to its safety and significant efficacy.
Oncolytic viruses (OVs), as a new class of anti-tumor immunotherapy drugs, have been known
by more and more people.
OVs are a class of viruses that are naturally or genetically engineered to selectively infect and kill tumor cells
.
OVs have precise oncolytic effect, can activate the immune response, and can be used in the treatment
of a variety of tumors.
H101 is ® the only OVs product
available in China.

In 2022, an article was published in the American Journal of Translational Research titled Advances in the clinical development of oncolytic The research of viruses mainly describes the progress of oncolytic virus clinical research at home and abroad, and evaluates the safety and efficacy
of oncolytic therapy for tumors.
As a professional journal of oncology, this journal has a high influence in the field of medicine, this paper collates the types, clinical stages, treatment methods and other detailed information of OVs, summarizes the clinical progress of OVs, and comprehensively analyzes
the safety and efficacy of tumor treatment.

Clinical staging of OVs

As of October 1, 2021, a total of 408 clinical studies of OVs have been conducted
.
Table 1 lists the clinical stages
of approximately 31 OVs products.
Of all anti-tumor clinical studies on OVs, phase I and II accounted for about 80% of all clinical studies; Phase III accounts for about 6% of all clinical studies, and most are still in their infancy
.
To date, DNA viruses account for 81.
4% of the total OVs, including adenovirus (41.
86%), herpes simplex virus (25.
58%) and vaccinia virus (13.
95%), and RNA virus accounts for 9.
3% (Figure 1).

NSCLC, Non-small cell lung cancer; OV, oncolytic virus.

Table 1 provides basic information on the current 31 OVs products

Figure 1.
Types of OVs in clinical studies

Treatment strategies for OVs

In the registered clinical trials, the treatment strategies of OVs were OVs monotherapy (36.
77%), oncolytic virus therapy combined with chemotherapy (18.
63%), immunotherapy (20.
83%).
, radiation therapy (3.
43%) or targeted therapy (0.
74%)
.
As shown in Figure 2, oncolytic virus combined immunity is the most commonly used combination therapy strategy
.

Figure 2.
OVs in combination with other therapies to treat tumors

OVs route of administration

Among the various routes of administration studied for global OVs, intratumoral injection accounted for 58.
6%, followed by intravenous injection (23.
03%)
.
According to the statistics on the distribution of drug routes in phase III clinical trials worldwide, intratumoral injection accounted for 46.
88% of all phase III studies, and intravenous injection accounted for 28.
13%.

Figure 3.
Proportion of OVs types in clinical studies

Antitumor efficacy of OVs

As of October 1, 2021, a total of 132 OVs clinical studies have been completed
.
Based on the results of the study, we found that OVs such as H101, T-VEC, G47Δ, hydrogen monoxide, T3011, and G47Δ have significant antitumor effects (Table 2).

MPE, malignant pleural effusion; HSV-1, herpes simplex virus type 1; GM-CSF, granulocyte-macrophage colony-stimulating factor; NMPA, National Medical ProductsAdministration; FDA, U.
S.
Food and Drug Administration; MHLW, Ministry of Health, Labor, and Welfare.

Table 2.
List of OVs products on the market

The development status of OVs in China

In 2018, Opdivo and Keytruda were approved for commercial use, boosting the development of
immunotherapy in China.
As an immunotherapy, OVs have a significant therapeutic effect on solid tumors, and their indications are constantly expanding
.
With the rapid development of China's medical field and the improvement of the government's supervision system for OVs industry, more than 10 kinds of OVs have been clinically studied in China (Table 3), which has broad application prospects
.
Toca511、 Reolysin, ADV-TK and E10A OVs have entered the phase III clinical phase
.

HSV, Herpes simplex virus.

Table 3.
Research on OVs projects in China

At present, H101 is the only OVs product listed in China, and its new indications are constantly being explored
.
Although evidence on H101 in combination with chemotherapy for patients with advanced nasopharyngeal carcinoma, as well as other solid tumors, has been accumulating for more than a decade, its underlying mechanisms and new clinical indications, including malignant pleural effusion, melanoma, liver cancer, and lung cancer, remain to be explored
.
Since 2019, basic and clinical research on H101 has made significant progress
.
A survey of recently registered clinical studies and related articles revealed that since 2019, there have been nine registered clinical studies on H101 for the treatment of tumors (Table 4) and 19 articles have been published (Table 5).

Table 4.
Clinical trials of H101 in recent years

IF, Impact Factor; SCI, Science Citation Index; ASCO, American Society of Clinical Oncology; CSCO, Chinese Society of Clinical Oncology; CSTPCD, Chinese Scientific Papers and Citation Database; PKU, Chinese Core Journal Criterion of Peking University.

Table 5.
Documents published on the H1020-2021 project

Professor Wang Baocheng, an oncologist at the 960th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, pointed out that since 2019, the Tianpu medical team has been focusing on exploring new ways of tumor treatment, and OVs have mild adverse reactions during anti-tumor treatment and high
patient compliance.
As the only OVs product successfully marketed in China, H101 has a significant
effect on the treatment of tumors.

In addition, Tianpu Pharmaceutical Medical Department also pays attention to the clinical research of oncolytic viruses, and its project "Oncolytic virus (recombinant human adenovirus type 5) tumor injection combined with radiotherapy for the treatment of refractory and relapsed and metastatic gynecological tumors" has been accepted by the 2022 ESMO Conference and CSCO Conference, and "PD1 monoclonal antibody combined with recombinant human adenovirus type 5 injection in patients with advanced malignant melanoma who have failed previous immunotherapy: an exploratory single-arm study" has been accepted by the 2022 ESMO Conference;

"Tislelizumab combined with recombinant human adenovirus type 5 injection in patients with advanced NSCLC who have failed prior immunotherapy: an exploratory single-arm study", "A single-center, single-arm, prospective study of recombinant adenovirus type 5 combined with FOLFOX hepatic arterial perfusion chemotherapy (HAIC) in the treatment of mass intrahepatic cholangiocarcinoma", "Efficacy and safety of recombinant human adenovirus type 5 injection in patients with advanced liver cancer with stable disease after sorafenib treatment: a prospective, randomized, Parallel controlled clinical studies", "Prospective and randomized controlled clinical study of recombinant human adenovirus type 5 injection combined with neoadjuvant chemotherapy for preoperative stage III lung cancer" and "Efficacy evaluation and benefit population screening of oncolytic virus H101 combined with carrelizumab in the treatment of recurrent cervical cancer" have also been accepted
by the 2022 CSCO conference.

Tianpu Pharmaceutical has always adhered to the principle of "patient-centered", improved the efficacy and safety of drugs, optimized the route of administration, found suitable biomarkers, and always regarded the efficacy and safety of anti-tumor as the focus
of research and development.
OVs can help patients achieve better personalized treatment of tumors, but the current research is still in its early stages, and more sustained efforts from industry colleagues are needed to help more patients recover
.

Professor Wang Baocheng

Chief physician, professor and doctoral supervisor of the 960th Hospital of the People's Liberation Army

Former vice president of the General Hospital of Jinan Military Region and director of the Institute of Oncology

Ph.
D.
, postdoctoral fellow in the United States

Army technical level 3 specialist

Recipients of special government allowances from the State Council

Winner of the third "Famous Doctor of the Country - Outstanding Achievements"

Executive Director of CSCO

Chairman of CSCO Immunotherapy Committee

Vice Chairman of the All-Army Oncology Committee

Health care consultation expert of the Central Military Commission

Vice President of Shandong Medical Association

Director of the National Agency for Clinical Validation of Drugs

Editor-in-Chief of Chinese Journal of Gastroenterology and Imaging

References:

[1] Li K, Zhao Y, Hu X, et al.
Advances in the clinical development of oncolytic viruses[J].
American Journal of Translational Research, 2022, 14(6): 4192.

[2] Yang YP.
Cancer immunotherapy: harnessing the immune system to battle cancer.
J Clin Invest 2015; 125: 3335-3337.

[3] Gujar S, Bell J and Diallo JS.
SnapShot: cancer immunotherapy with oncolytic viruses.
Cell 2019; 176: 1240-1240, e1.

[4] Goradel NH, Baker AT, Arashkia A, Ebrahimi N, Ghorghanlu S and Negahdari B.
Oncolytic virotherapy: challenges and solutions.
Curr Probl Cancer 2021; 45: 100639.

[5] Twumasi-Boateng K, Pettigrew JL, Kwok YYE, Bell JC and Nelson BH.
Oncolytic viruses as en-gineering platforms for combination immunotherapy.
Nat Rev Cancer 2018; 18: 419-432.

[6] Wang XK, Shao XY, Gu L, Jiang K, Wang ST, Chen JH, Fang JM, Guo XL, Yuan M, Shi J, Ding C, Meng SS and Xu Q.
Targeting STAT3 enhances NDV-induced immunogenic cell death in prostate cancer cells.
J Cell Mol Med 2020; 24: 4286-4297.

[7] Breitbach CJ, Arulanandam R, De Silva N, Thorne SH, Patt R, Daneshmand M, Moon A, Ilkow C, Burke J, Hwang TH, Heo J, Cho M, Chen H, Angarita FA, Addison C, McCart JA, Bell JC and Kirn DH.
Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans.
Cancer Res 2013; 73: 1265-1275.

[8] Macedo N, Miller DM, Haq R and Kaufman HL.
Clinical landscape of oncolytic virus research in 2020.
J Immunother Cancer 2020; 8: e001486.

[9] Shao XY, Wang XK, Guo XL, Jiang K, Ye T, Chen JH, Fang JM, Gu L, Wang ST, Zhang GR, Meng SS and Xu Q.
STAT3 contributes to oncolytic newcastle disease virus-induced immunogenic cell death in melanoma cells.
Front Oncol 2019; 9: 436.

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