Oncolytic adenovirus <scp>H101</scp> ameliorate the efficacy of <scp>anti‐PD</scp>‐1 monotherapy in colorectal cancer

Huang, Lili; Zhao, Huaxin; Shan, Mengying; Chen, Hong; Xu, Bin; He, Yang; Zhao, Yu; Liu, Zhuqing; Chen, Jianhua; Xu, Qing

doi:10.1002/cam4.4845

Cited by 10 publications

(4 citation statements)

References 40 publications

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“…For Ad therapies, the liver is a considerable sink for Ad that reach the systemic circulation, which may diminish therapeutic efficacy [ 33 , 34 ]. Oncolytic viruses are commonly injected intratumorally to achieve high levels in the injected tumor(s) while minimizing off-target activity [ 55 , 56 , 57 ]. With CAR-negative CT26 tumors, intratumoral injection nevertheless resulted in poor transduction of the tumor and primarily led to off-target transduction in the liver.…”

Section: Discussionmentioning

confidence: 99%

Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes

et al. 2022

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Adenovirus (Ad) is a widely studied viral vector for cancer therapy as it can be engineered to cause selective lysis of cancer cells. However, Ad delivery is limited in treating cancers that do not have coxsackievirus and adenovirus receptors (CAR). To overcome this challenge, Ad-encapsulated liposomes were developed that enhance the delivery of Ads and increase therapeutic efficacy. Cationic empty liposomes were manufactured first, to which an anionic Ad were added, which resulted in encapsulated Ad liposomes through charge interaction. Optimization of the liposome formula was carried out with series of formulation variables experiments using an extrusion process, which is ideal for laboratory-scale small batches. Later, the optimized formulation was manufactured with a homogenization technique—A high shear rotor-stator blending, that is ideal for large-scale manufacturing and is in compliance with Good Manufacturing Practices (GMP). Comparative in vitro transduction, physicochemical characterization, long-term storage stability at different temperature conditions, and in vivo animal studies were performed. Ad encapsulated liposomes transduced CAR deficient cells 100-fold more efficiently than the unencapsulated Ad (p ≤ 0.0001) in vitro, and 4-fold higher in tumors injected in nude mice in vivo. Both extrusion and homogenization performed similarly–with equivalent in vitro and in vivo transduction efficiencies, physicochemical characterization, and long-term storage stability. Thus, two Ad encapsulated liposomes preparation methods used herein, i.e., extrusion vs. homogenization were equivalent in terms of enhanced Ad performance and long-term storage stability; this will, hopefully, facilitate translation to the clinic.

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Section: Discussionmentioning

confidence: 99%

Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes

et al. 2022

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“…Recombinant human adenovirus type 5 (H101, also known as Oncorine), a genetically modified oncolytic adenovirus, has demonstrated clinical efficacy for treating various malignancies. 9–11 Huang et al, 12 confirmed that H101 ameliorated the efficacy of anti-PD-1 monotherapy in CRC. Herein, this report details a case of substantial abdominal lymph node metastasis, measuring 12 cm in diameter, following CRC surgery.…”

Section: Introductionmentioning

confidence: 91%

A Case Report of Pathologically Complete Response of a Huge Lymph Node Metastasis of Colorectal Cancer After Treatment with Intratumoral Oncolytic Virus H101 and Capecitabine

Wang,

Zhang

2024

ITT

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“…Another study using an E1A delta24 OAd expressing a modified version of PD-1 (Ad-CAB) demonstrated excellent immune cell killing of tumor cell both with small cell lung carcinoma [ 32 ]. Combination of H101 with anti-PD-1 therapy was shown to enhance anti-tumor response in murine colorectal cancer [ 33 ].…”

Section: Combining Oncolytic Adenovirus With Immune Checkpoint Inhibi...mentioning

confidence: 99%

A Renaissance for Oncolytic Adenoviruses?

Blanchette

Teodoro

2023

Viruses

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In the 1990s, adenovirus became one of the first virus types to be genetically engineered to selectively destroy cancer cells. In the intervening years, the field of “oncolytic viruses” has slowly progressed and culminated in 2015 with the FDA approval of Talimogene laherparepvec, a genetically engineered herpesvirus, for the treatment of metastatic melanoma. Despite the slower progress in translating oncolytic adenovirus to the clinic, interest in the virus remains strong. Among all the clinical trials currently using viral oncolytic agents, the largest proportion of these are using recombinant adenovirus. Many trials are currently underway to use oncolytic virus in combination with immune checkpoint inhibitors (ICIs), and early results using oncolytic adenovirus in this manner are starting to show promise. Many of the existing strategies to engineer adenoviruses were designed to enhance selective tumor cell replication without much regard to interactions with the immune system. Adenovirus possesses a wide range of viral factors to attenuate both innate anti-viral pathways and immune cell killing. In this review, we summarize the strategies of oncolytic adenoviruses currently in clinical trials, and speculate how the mutational backgrounds of these viruses may impact upon the efficacy of these agents in oncolytic and immunotherapy. Despite decades of research on human adenoviruses, the interactions that these viruses have with the immune system remains one of the most understudied aspects of the virus and needs to be improved to rationally design the next generation of engineered viruses.

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Oncolytic adenovirus H101 ameliorate the efficacy of anti‐PD‐1 monotherapy in colorectal cancer

Cited by 10 publications

References 40 publications

Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes

Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes

A Case Report of Pathologically Complete Response of a Huge Lymph Node Metastasis of Colorectal Cancer After Treatment with Intratumoral Oncolytic Virus H101 and Capecitabine

A Renaissance for Oncolytic Adenoviruses?

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