Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles

Asavarut, Paladd; Waramit, Sajee; Suwan, Keittisak; Marais, Gert; Chongchai, Aitthiphon; Benjathummarak, Surachet; Al-Bahrani, Mariam; Vila-Gómez, Paula; Williams, Matthew; Kongtawelert, Prachya; Yata, Teerapong; Hajitou, Amin

doi:10.15252/emmm.202115418

Cited by 17 publications

(50 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Asavarut and colleagues combined the benefits of phage and rAAV technology to create transmorphic phage/AAV (TPA) particles. These can effectively target tumor cells in vitro and in vivo to deliver immunotherapy genes, while simultaneously having no negative effects on healthy tissues ( 28 ). Kuklik et al developed a bispecific antibody-based gene delivery method in the absence of a new tissue-specific AAV vector, suggesting that redirecting AAVs to particular target receptors are possible ( 29 ).…”

Section: Aav and Aav Vectorsmentioning

confidence: 99%

See 1 more Smart Citation

Adeno-associated virus vector-mediated gene therapy for the treatment of ovarian cancer: a literature review

Zhu¹,

Qin²,

Wei³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background and Objective: The adeno-associated virus (AAV) is a member of the Parvoviridae family and has emerged as one of the most popular and promising approaches for gene therapy due to its low toxicity, low immunogenicity, and excellent safety after optimization. Advances in gene therapy methods have allowed novel treatments such as using AAV to knock out or repair target genes. AAV-mediated gene therapy has been used in numerous tumor studies, including lymphatic metastasis of prostate cancer, liver cancer, and renal cell carcinoma in mice. Ovarian cancer is an extremely aggressive malignancy which is prone to recurrence, and AAV vector-based gene therapy may be a potential treatment strategy.Methods: Herein, we reviewed the current research to provide an update on the role of AAV-mediated gene therapy in tumor research, especially in ovarian cancer. To find recent developments in pertinent research, we examined the PubMed database.Key Content and Findings: AAV vectors may produce steady and effective gene expression without becoming harmful, making it a viable gene delivery technique. AAV-based gene therapy products have been widely used in preclinical research and some have achieved marketing approval.Conclusions: Due to its affinity for various organs, reliable integration, and long-lasting expression, certain AAV serotypes have been widely used in gene therapy. However, there are also some challenges.Extensive research on the role of AAV in disease and gene therapy has shown great potential. Herein, we examined the literature to better understand the function of the AAV in tumor research, particularly in ovarian cancer research.

show abstract

Section: Aav and Aav Vectorsmentioning

confidence: 99%

“…tissues(28). Kuklik et al developed a bispecific antibodybased gene delivery method in the absence of a new tissuespecific AAV vector, suggesting that redirecting AAVs to particular target receptors are possible(29).…”

mentioning

confidence: 99%

Adeno-associated virus vector-mediated gene therapy for the treatment of ovarian cancer: a literature review

Zhu¹,

Qin²,

Wei³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…In this study, we used the recently reported TPA particles characterized by enhanced gene expression, high titer production and large DNA sequence accommodation [9], then constructed the RGD4C.TPA.TNFα (Fig. 1) to evaluate the efficacy of guided systemic delivery of TNF gene for medulloblastoma treatment.…”

Section: Introductionmentioning

confidence: 99%

“…As a tool for targeted and efficient gene delivery, bacteriophage-based vectors have proven their application in prostate and breast cancers, soft tissue sarcomas, gliomas, and pancreatic cancer [10][11][12][13][14] by using a hybrid phage vector, which was previously constructed by incorporating within the phage genome a mammalian transgene expression cassette flanked by inverted terminal repeats (ITRs) from the adeno-associated virus AAV2 [15]. Recently we reported a new generation of phage-based particles for targeted systemic gene delivery consisting of the packaging a recombinant rAAV2 DNA by coat proteins of a filamentous phage, named transmorphic phage/AAV, or TPA [9]. In the TPA particles, the phage genome was removed and an f1 origin of replication is the only remaining phage cis element to allow replication of the single stranded ITR-flanked transgene expression cassette in bacteria and its packaging into the phage capsid provided through infection by a helper phage [9].…”

Section: Introductionmentioning

confidence: 99%

“…Recently we reported a new generation of phage-based particles for targeted systemic gene delivery consisting of the packaging a recombinant rAAV2 DNA by coat proteins of a filamentous phage, named transmorphic phage/AAV, or TPA [9]. In the TPA particles, the phage genome was removed and an f1 origin of replication is the only remaining phage cis element to allow replication of the single stranded ITR-flanked transgene expression cassette in bacteria and its packaging into the phage capsid provided through infection by a helper phage [9]. The helper was modified to display the double cyclic RGD4C (CDCRGDCFC) ligand on its pIII minor coat proteins to specifically target tumors by binding to the α v β 3 integrin receptor, and at a lower extent to α v β 5 [16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transmorphic phage-guided systemic delivery ofTNFαgene for the treatment of human paediatric medulloblastoma

Al-Bahrani

Waramit

Suwan

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Medulloblastoma is the most common childhood brain tumor with an unfavorable prognosis and limited options of harmful treatments that are associated with devastating long-term side effects. Therefore, the development of safe, non-invasive and effective therapeutic approaches is required to save the quality of life of young medulloblastoma survivors. We postulated that therapeutic targeting is a solution. Thus, we used a recently designed tumor-targeted bacteriophage (phage)-derived particle, named transmorphic phage/AAV, TPA, to deliver a transgene expressing the tumor necrosis factor alpha (TNFα) for targeted systemic therapy of medulloblastoma. This vector was engineered to display the double cyclic RGD4C peptide to selectively target tumors after intravenous administration. Furthermore, the lack of native phage tropism to mammalian cells warrants safe and selective systemic delivery to the tumor microenvironment. In vitro RGD4C.TPA.TNFα treatment of human medulloblastoma cells generated efficient and selective TNFα expression, subsequently triggering cell death. Combination with the chemotherapeutic drug cisplatin, used clinically against medulloblastoma, resulted in augmented effect through the enhancement of TNFα gene expression. Systemic administration of RGD4C.TPA.TNFα to mice bearing subcutaneous medulloblastoma xenografts resulted in selective tumor homing of these particles, and consequently targeted tumor expression of TNFα, apoptosis, and destruction of the tumor vasculature. Thus, our RGD4C.TPA.TNFα particle provides selective and efficient systemic delivery of TNFα to medulloblastoma, yielding a potential TNFα anti-medulloblastoma therapy while sparing healthy tissues from the systemic toxicity of this cytokine.

show abstract

Utilizing adeno‐associated virus as a vector in treating genetic disorders or human cancers

Shih,

Chang,

Wang

2024

IUBMB Life

View full text Add to dashboard Cite

Clinical data from over two decades, involving more than 3000 treated patients, demonstrate that adeno‐associated virus (AAV) gene therapy is a safe, effective, and well‐tolerated therapeutic method. Clinical trials using AAV‐mediated gene delivery to accessible tissues have led to successful treatments for numerous monogenic disorders and advancements in tissue engineering. Although the US Food and Drug Administration (FDA) has approved AAV for clinical use, systemic administration remains a significant challenge. In this review, we delve into AAV biology, focusing on current manufacturing technologies and transgene engineering strategies. We examine the use of AAVs in ongoing clinical trials for ocular, neurological, and hematological disorders, as well as cancers. By discussing recent advancements and current challenges in the field, we aim to provide valuable insights for researchers and clinicians navigating the evolving landscape of AAV‐based gene therapy.

show abstract

Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles

Cited by 17 publications

References 81 publications

Adeno-associated virus vector-mediated gene therapy for the treatment of ovarian cancer: a literature review

Adeno-associated virus vector-mediated gene therapy for the treatment of ovarian cancer: a literature review

Transmorphic phage-guided systemic delivery ofTNFαgene for the treatment of human paediatric medulloblastoma

Utilizing adeno‐associated virus as a vector in treating genetic disorders or human cancers

Contact Info

Product

Resources

About