Interaction of adenovirus with antibodies, complement, and coagulation factors

Allen, Rondine J.; Byrnes, Andrew P.

doi:10.1002/1873-3468.13649

Cited by 39 publications

(30 citation statements)

References 98 publications

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“…Besides binding to coagulation proteins with g-carboxyglutamic acid (GLA) domains, adenoviral particles bind complement component C3 and natural immunoglobulin (Ig)M antibodies, resulting for instance in neutrophil activation. [8][9][10][11][12] Antibody-virus complexes can trigger inflammatory cytokine and chemokine responses in macrophages through the intracellular antibody receptor TRIM21. [13][14][15][16] Interestingly, binding of FX appears to compete with adenoviral interactions with complement and antibodies, shielding it from these components while subsequently promoting TLR4 signaling in the spleen.…”

Section: Early Innate Responses To Systemically Delivered Admentioning

confidence: 99%

Immune Responses to Viral Gene Therapy Vectors

et al. 2020

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Several viral vector-based gene therapy drugs have now received marketing approval. A much larger number of additional viral vectors are in various stages of clinical trials for the treatment of genetic and acquired diseases, with many more in pre-clinical testing. Efficiency of gene transfer and ability to provide long-term therapy make these vector systems very attractive. In fact, viral vector gene therapy has been able to treat or even cure diseases for which there had been no or only suboptimal treatments. However, innate and adaptive immune responses to these vectors and their transgene products constitute substantial hurdles to clinical development and wider use in patients. This review provides an overview of the type of immune responses that have been documented in animal models and in humans who received gene transfer with one of three widely tested vector systems, namely adenoviral, lentiviral, or adeno-associated viral vectors. Particular emphasis is given to mechanisms leading to immune responses, efforts to reduce vector immunogenicity, and potential solutions to the problems. At the same time, we point out gaps in our knowledge that should to be filled and problems that need to be addressed going forward.

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Section: Early Innate Responses To Systemically Delivered Admentioning

confidence: 99%

Immune Responses to Viral Gene Therapy Vectors

et al. 2020

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“…The interactions impacting Ad biodistribution upon intravascular delivery have been widely described. Reasons for the low efficacy of Ad5-derived vectors include clearance after opsonization by natural antibodies and complement, as well as sequestration in the liver and spleen mediated by binding with human coagulation factor 10 (FX) and other coagulation factors to HSPG abundant on hepatocytes or scavenger receptors on Kupffer cells [136][137][138]. Since a small portion of the Ad particles injected ip are able to enter the circulation, Ad vectors administered through this route are susceptible to clearance after interacting with blood components and residential macrophages in tissue and in the peritoneal cavity [83,139].…”

Section: Overcoming Physical Barriers To Dissemination Of Oncolytic Amentioning

confidence: 99%

Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer

2020

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Ovarian cancer is the leading cause of death among women with gynecological cancer, with an overall 5-year survival rate below 50% due to a lack of specific symptoms, late stage at time of diagnosis and a high rate of recurrence after standard therapy. A better understanding of heterogeneity, genetic mutations, biological behavior and immunosuppression in the tumor microenvironment have allowed the development of more effective therapies based on anti-angiogenic treatments, PARP and immune checkpoint inhibitors, adoptive cell therapies and oncolytic vectors. Oncolytic adenoviruses are commonly used platforms in cancer gene therapy that selectively replicate in tumor cells and at the same time are able to stimulate the immune system. In addition, they can be genetically modified to enhance their potency and overcome physical and immunological barriers. In this review we highlight the challenges of adenovirus-based oncolytic therapies targeting ovarian cancer and outline recent advances to improve their potential in combination with immunotherapies.

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“…There is some interest in interactions between the major protein systems contained in circulating plasma. The focus on such intravascular reactions ranges from potential importance in severe systemic diseases [11, 12] to possibility for virus vector treatments to evade the complex plasma protein milieu [13]. However, the aim of this review is to provide in vivo data, including well-controlled observations in human airways, requiring that further questions be asked:…”

Section: Introductionmentioning

confidence: 99%

Humoral First-Line Mucosal Innate Defence in vivo

Persson¹

2020

J Innate Immun

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Based on observations in vivo in guinea-pig and human airways, this review presents plasma exudation as non-sieved transmission of bulk plasma across an unperturbed mucosa that maintains its normal barrier functions. Several steps have led to the present understanding of plasma exudation as a non-injurious response to mucosal challenges. The implication of a swift appearance of all circulating multipotent protein systems (also including antimicrobial peptides that now are viewed as being exclusively produced by local cells) on challenged, but intact, mucosal surfaces cannot be trivial. Yet, involvement of early plasma exudation responses in innate mucosal immunology has dwelled below the radar. Admittedly, exploration of physiological plasma exudation mechanisms requires in vivo approaches beyond mouse studies. Plasma exudation also lacks the specificity that is a hallmark of biological revelations. These aspects separate plasma exudation from mainstream progress in immunology. The whole idea, presented here, thus competes with strong paradigms currently entertained in the accepted research front. The present focus on humoral innate immunity in vivo further deviates from most discussions, which concern cell-mediated innate defence. Indeed, plasma exudation has emerged as sole in vivo source of major mucosal defence proteins that now are viewed as local cell produce. In conclusion, this review highlights opportunities for complex actions and interactions provided by non-sieved plasma proteins/peptides on the surface of intact mucosal barriers in vivo.

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Interaction of adenovirus with antibodies, complement, and coagulation factors

Cited by 39 publications

References 98 publications

Immune Responses to Viral Gene Therapy Vectors

Immune Responses to Viral Gene Therapy Vectors

Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer

Humoral First-Line Mucosal Innate Defence in vivo

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