Nonhuman Primate Adenoviruses of the Human Adenovirus B Species Are Potent and Broadly Acting Oncolytic Vector Candidates

Bots, Selas T. F.; Kemp, Vera; Cramer, Steve; Wollenberg, Diana J.M. van den; Hornsveld, Marten; Lamfers, Martine L.M.; Pluijm, Gabri van der; Hoeben, Rob C.

doi:10.1089/hum.2021.216

Cited by 8 publications

(26 citation statements)

References 62 publications

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“…The isolation of the new AdV isolates analyzed here was described previously [ 20 ]. Out of 41 new and unique isolates, 29 clustered with the HAdV-C species in a comparison of the nucleotide sequences of region coding for their hypervariable regions 1–7 of the hexon gene.…”

Section: Resultsmentioning

confidence: 99%

“…The HAdV-C5 E1 transformed human embryonic retinoblast cell line HER911 was used for the isolation and propagation of the non-human primate-derived AdVs as described [ 20 , 33 ]. The HER911 cells were cultured in high glucose Dulbecco’s Modified Eagle’s Medium (DMEM, Gibco, Carlsbad, MA, USA) supplemented with 8% fetal bovine serum (FBS, Invitrogen, Carlsbad, MA, USA) and 1% Penicillin-Streptomycin (P/S, Gibco).…”

Section: Methodsmentioning

confidence: 99%

“…Fecal samples were obtained from Gorilla gorilla gorilla (Western lowland gorilla), Pan troglodytes (chimpanzee), Pan paniscus (bonobo), and Pongo pygmaeus (Bornean orangutan) held in captivity in Dutch zoos. The viruses were isolated as described [ 23 ] with the modifications described previously [ 20 ]. Briefly, aliquots of 250–500 mg feces were dispersed in 5 mL phosphate-buffered saline without Ca 2+ and Mg 2+ (PBS − ) and the suspension was cleared by centrifugation.…”

Section: Methodsmentioning

confidence: 99%

“…For isolation of hexon hypervariable regions of DNA for sequencing, 100 µL of virus-containing supernatant was added to near-confluent cultures of HER911 cells. Once CPE became apparent, cells and medium were collected and used for a modified Hirt DNA extraction procedure optimized for AdV DNA isolation as described [ 20 ]. Approximately 10 ng of DNA was used for PCR amplification of the hexon hypervariable region (HHVR) 1–7 using the following primers: 5′-CAGGATGCTTCGGAGTACCTGAG-3′ (forward primer), and 5′-TTGGCNGGDATDGGGTAVAGCATGTT-3′ (reverse primer).…”

Section: Methodsmentioning

confidence: 99%

“…Non-human primate AdVs have been explored as gene-transfer vectors to which low levels of neutralizing immunity exists in the human population [ 16 , 19 ]. To expand the collection of available non-human primate AdVs, we isolated new AdVs from healthy western lowland gorillas, bonobos, chimpanzees, and orangutans kept in Dutch zoos [ 20 ]. This yielded 41 unique isolates, as based on sequencing of the hypervariable regions 1–7 of the hexon gene.…”

Section: Introductionmentioning

confidence: 99%

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Genome Analyses of Ten New Ape Adenoviruses with Similarity to Human Mastadenovirus C

Bots

Kemp

Dautzenberg

et al. 2022

IJMS

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The adenoviruses (AdVs) isolated from humans are taxonomically grouped in seven different species in the Mastadenovirus genus (HAdV-A through G). AdVs isolated from apes are often included in one of the human AdV species. Here we describe the sequence analyses of ten new AdVs that are related to the HAdV-C species and that were isolated from healthy western lowland gorillas, bonobos, chimpanzees, and orangutans kept in Dutch zoos. We analyzed these viruses and compared their genome sequences to those of human- and ape-derived AdV sequences in the NCBI GenBank database. Our data demonstrated that the ape-derived viruses clustering to HAdV-C are markedly distinct from the human HAdV-C species in the size and nucleotide composition (%GC) of their genome, differ in the amino-acid sequence of AdV proteins, and have longer RGD-loops in their penton-base proteins. The viruses form three well-separated clades (the human, the gorilla, and the combined group of the bonobo and chimpanzee viruses), and we propose that these should each be given species-level ranks. The Ad-lumc005 AdV isolated from orangutans was found to be very similar to the gorilla AdVs, and bootstrap inference provided evidence of recombination between the orangutan AdV and the gorilla AdVs. This suggests that this virus may not be a genuine orangutan AdV but may have been transferred from a gorilla to an orangutan host.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genome Analyses of Ten New Ape Adenoviruses with Similarity to Human Mastadenovirus C

Bots

Kemp

Dautzenberg

et al. 2022

IJMS

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Preclinical evaluation of the gorilla‐derived HAdV‐B AdV‐lumc007 oncolytic adenovirus ‘GoraVir’ for the treatment of pancreatic ductal adenocarcinoma

Bots,

Harryvan,

Groeneveldt

et al. 2024

Molecular Oncology

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance due to its genetic and cellular heterogeneity, dense stromal tissue, and immune‐suppressive tumor microenvironment. Oncolytic virotherapy has emerged as a new treatment modality which uses tumor‐specific viruses to eliminate cancerous cells. Non‐human primate adenoviruses of the human adenovirus B (HAdV‐B) species have demonstrated considerable lytic potential in human cancer cells as well as limited preexisting neutralizing immunity in humans. Previously, we have generated a new oncolytic derivative of the gorilla‐derived HAdV‐B AdV‐lumc007 named ‘GoraVir’. Here, we show that GoraVir displays oncolytic efficacy in pancreatic cancer cells and pancreatic‐cancer‐associated fibroblasts. Moreover, it retains its lytic potential in monoculture and co‐culture spheroids. In addition, we established the ubiquitously expressed complement receptor CD46 as the main entry receptor for GoraVir. Finally, a single intratumoral dose of GoraVir was shown to delay tumor growth in a BxPC‐3 xenograft model at 10 days post‐treatment. Collectively, these data demonstrate that the new gorilla‐derived oncolytic adenovirus is a potent oncolytic vector candidate that targets both pancreatic cancer cells and tumor‐adjacent stroma.

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Viral vector‐based cancer treatment and current clinical applications

Xie,

Han,

Liu

et al. 2023

MedComm – Oncology

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Owing to the limitations of conventional cancer therapies, including chemotherapy, radiotherapy, and surgery, gene therapy has become a prominent strategy for cancer treatment over the past few decades. Gene therapy is a medical approach for targeting and destroying cancer cells by delivering exogenous genes into the target cancerous cells or surrounding tissues. However, successful delivery of foreign genes into target cells and tissues remains a key issue in such therapy. Efficient gene delivery systems would undoubtedly be important for improving the medical outcomes of gene therapy. With genetic modifications, viral vectors can target specific cells with high gene transduction efficiency, thus, the use of viral vectors is a promising technology for improving foreign gene delivery. Currently, four viral vectors—adenovirus, adeno‐associated virus, herpes simplex virus, and retrovirus—are dominantly being investigated and used in preclinical and clinical trials. In this review, we provide an overview of the mechanisms and latest applications of the four above‐mentioned viral vectors, and summarize the current development of several other viral vectors. In addition, we discuss the challenges and provide insights into future development of viral vectors in cancer treatment.

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Nonhuman Primate Adenoviruses of the Human Adenovirus B Species Are Potent and Broadly Acting Oncolytic Vector Candidates

Cited by 8 publications

References 62 publications

Genome Analyses of Ten New Ape Adenoviruses with Similarity to Human Mastadenovirus C

Genome Analyses of Ten New Ape Adenoviruses with Similarity to Human Mastadenovirus C

Preclinical evaluation of the gorilla‐derived HAdV‐B AdV‐lumc007 oncolytic adenovirus ‘GoraVir’ for the treatment of pancreatic ductal adenocarcinoma

Viral vector‐based cancer treatment and current clinical applications

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