DNA Vaccination with Electroporation Induces Increased Antibody Responses in Patients with Prostate Cancer

Low, Lindsey; Mander, Ann; McCann, Katy J.; Dearnaley, David P.; Tjelle, Torunn Elisabeth; Mathiesen, Iacob; Stevenson, Freda K.; Ottensmeier, Christian

doi:10.1089/hum.2009.067

Cited by 169 publications

(126 citation statements)

References 33 publications

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“…15 Recently, clinical trials have showed the efficiency of EP in humans. 16,17 Our data confirmed that EP in more efficient than IM injection. Indeed, quite disappointing results were obtained after using a conventional IM vaccination schedule (data not shown), whereas a short vaccination program by EP and ID injection 15 gave rise to strong humoral response by ss-linked constructs.…”

Section: Discussionsupporting

confidence: 80%

A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines

Massa

Paolini²,

Curzio³

et al. 2017

Human Vaccines & Immunotherapeutics

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Signal sequences (ss) play a critical role in the sorting of nascent secretory and membrane proteins. This function has been conserved from bacteria through eukaryotes, although ss appear diverse in length and amino acid composition. Sorting of proteins is also critical to instruct antigens for a proper immunological response. Thus, a plant ss was used to drive Human Papillomavirus (HPV) model antigens into the human secretory pathway: the HPV16 E7 oncoprotein, its chimera with the coat protein (CP) of the Potato Virus X (PVX), the first 200 amino acids of the HPV16 minor capsid protein L2 (known to harbour cross-reacting epitopes) and its chimera with E7 gene. These genes were used to transfect HEK-293 cells and to immunize C57BL/6 mice. The ss-provided genes were expressed, and proteins detected by immunofluorescence and immunoblotting. Mouse immunization with DNA constructs carrying the ss elicited a strong humoral response against both E7 and L2 and a weak cell-mediated immunity.To our knowledge this is the first demonstration that a signal sequence derived from a plant can modulate the sorting of a heterologous protein in mammalian cells. This activity in mammalian cells may be responsible for the observed increased humoral response to DNA-based vaccines that are generally weak inducers of IgG response. This might open new perspectives in the design of DNA vaccines, especially to counteract infections where a strong humoral response is needed.

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Section: Discussionsupporting

confidence: 80%

A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines

Massa

Paolini²,

Curzio³

et al. 2017

Human Vaccines & Immunotherapeutics

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“…Mechanisms to increase their potency have been reviewed and include delivery by electroporation and using DNA vaccines in the context of a heterologous prime: boost strategy (Stevenson et al, 2010). Electroporation improves DNA vaccine activity by enhancing antigen expression as well as increasing inflammatory milieu (Best et al, 2009;Low et al, 2009;Roos et al, 2009). Using viral vectors to boost primary plasmid DNA vaccines has proven effective for infectious disease such as malaria (Gilbert et al, 2006) and is thought to focus the immune effector response against the intended target organism as opposed to transfected myocytes or APCs.…”

Section: Possible Immunological Reasons For Lack Of Efficacymentioning

confidence: 99%

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

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Canine melanoma as a model of human melanomaFor at least two decades, veterinary oncologists have advocated using spontaneously occurring tumours in companion animals as models for human cancer (Knapp and Waters, 1997;MacEwen, 1990). Several recent reviews have readdressed this approach identifying osteosarcoma, mammary tumours, head and neck cancers, bladder carcinomas, non-Hodgkin lymphoma, prostatic carcinoma, lung cancer and pertinently oral canine malignant melanoma (CMM) as good models for human neoplasms (Hansen and Khanna, 2004;Khanna and Hunter, 2005;Paoloni and Khanna, 2008). The major benefits of dogs as tumour models include the ability to study genetically outbred and immunologically intact animals in which cancers develop spontaneously and thus, more likely reflect the process of tumourigenesis compared to experimentally-induced neoplasms. As pets and owners share the same environment, they may be exposed to the same carcinogens, which, in part, drive tumour development. Regarding disease modelling, animal tumours often have similar clinical presentation, tumour biology and histopathological appearance to their human counterparts and usually progress more rapidly, thereby shortening data maturation times. In addition, few "standard of care" therapies exist for dogs meaning that within reason, trial therapeutics can be instigated at any point. Given these benefits, companion animal tumour models more accurately reflect the features of human cancers compared to rodent models with CMM being a desirable example of one such neoplasm. Conversely, the opportunity to translate the potential value of state of the art human therapeutics to the veterinary clinic also exists. Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics.

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“…Electroporation is recognized as one powerful way in which this can be achieved in the clinic. 34,35 However, electroporation requires the availability of specialized equipment. Combining plasmid DNA with a synthetic polymer to form a complex before administration to the patient can facilitate the entry of DNA into the cell, thus improving antigen expression, and represents an easily accessible and a convenient alternative.…”

Section: Discussionmentioning

confidence: 99%

Phase I clinical trial of idiotypic DNA vaccine administered as a complex with polyethylenimine to patients with B-cell lymphoma

Meleshko

Petrovskaya

Savelyeva

et al. 2017

Human Vaccines & Immunotherapeutics

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We report on the design of a phase I, non-randomized, open-label study of idiotypic DNA vaccination in patients with B-cell non-Hodgkin's lymphoma (ISRCTN31090206). The study uses DNA fusion gene vaccination encoding patient-specific single chain variable fragment, or idiotype, linked to an immunostimulatory sequence. Two types of immunostimulatory sequence are being explored: potato virus X coat protein and human chemokine MIP3a. Linear polyethylenimine with low molecular weight (8 kDa) is used as a synthetic vehicle for vaccine delivery. Humoral and T-cellular immune responses to vaccination will be measured by ELISA and ELISPOT, respectively. The primary study endpoints are safety, tolerability and immunogenicity of DNA-PEI vaccination.

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DNA Vaccination with Electroporation Induces Increased Antibody Responses in Patients with Prostate Cancer

Cited by 169 publications

References 33 publications

A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines

A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines

Cancer immunology and canine malignant melanoma: A comparative review

Phase I clinical trial of idiotypic DNA vaccine administered as a complex with polyethylenimine to patients with B-cell lymphoma

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