Transcutaneous Immunization with Cytotoxic T-Cell Peptide Epitopes Provides Effective Antitumor Immunity in Mice

Itoh, Tsuyoshi; Celis, Esteban

doi:10.1097/01.cji.0000171289.78495.b0

Cited by 37 publications

(26 citation statements)

References 17 publications

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“…However, more attention has been paid to topical administration of imidazoquinolines, evaluated in OVA, HIV-1, and melanoma models. With this application method, effective anti-OVA or antitumor immune responses were also elucidated, even when OVA peptides were delivered transcutaneously together with imiquimod in an ointment [65,140,141]. Craft et al [78] observed that the antitumor activity of imiquimod was not dependent on direct application of imiquimod to the tumor site, whereas Tomai et al [142] reported that the greater Th1 antibody response was only found if resiquimod was applied at the vaccination site.…”

Section: How Can Cancer Vaccine Approaches Benefit From Tlr7/8 Ligands?mentioning

confidence: 99%

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

et al. 2008

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After completing this course, the reader should be able to:1. Describe the subtypes of Toll-like receptor 7 and 8 agonists and their effect on the different components of the antitumor immune response.2. Argue why they are used as stand-alone immunotherapeutic agents.3. Evaluate their potential to improve current approaches of active and passive immunotherapy.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACT

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Section: How Can Cancer Vaccine Approaches Benefit From Tlr7/8 Ligands?mentioning

confidence: 99%

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

et al. 2008

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“…Although several reports describe epicutaneous priming of CD8 T cells (4,5,(7)(8)(9), there is considerable variability in the timing and approach used to determine the T-cell response and the use of skin preconditioning (such as tape stripping and acetone treatment) before immunization. This has made it difficult to compare the efficacy of distinct adjuvants.…”

Section: Epicutaneous Vaccination Using Cpg and Cholera Toxin As Adjumentioning

confidence: 99%

“…These include toll-like receptor (TLR) agonists such as imiquimod and CpG (6)(7)(8)(9), but also the ADP ribosylating bacterial exotoxins such as cholera toxin (CT) and the closely related Escherichia coli heat-labile enterotoxin (LT) (10)(11)(12). Application of such toxins to the skin is safe and effective in priming humoral and cellular responses in both mice and humans (4,10,(13)(14)(15).…”

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confidence: 99%

Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination

Olvera-Gómez

Hamilton

Xiao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The ability to induce humoral and cellular immunity via antigen delivery through the unbroken skin (epicutaneous immunization, EPI) has immediate relevance for vaccine development. However, it is unclear which adjuvants induce protective memory CD8 T-cell responses by this route, and the molecular and cellular requirements for priming through intact skin are not defined. We report that cholera toxin (CT) is superior to other adjuvants in its ability to prime memory CD8 T cells that control bacterial and viral challenges. Epicutaneous immunization with CT does not require engagement of classic toll-like receptor (TLR) and inflammasome pathways and, surprisingly, is independent of skin langerin-expressing cells (including Langerhans cells). However, CT adjuvanticity required type-I IFN sensitivity, participation of a Batf3-dependent dendritic cell (DC) population and engagement of CT with suitable gangliosides. Chemoenzymatic generation of CT-antigen fusion proteins led to efficient priming of the CD8 T-cell responses, paving the way for development of this immunization strategy as a therapeutic option. M ost current vaccination methods involve intramuscular or intradermal injection of antigen with suitable adjuvants. However, this approach produces biohazardous needle waste, requires trained personnel for its implementation, and evokes needle phobia, a significant complication that reduces compliance (1). Transdermal or epicutaneous immunization (EPI) strategies aim to avoid these concerns through application of antigen and adjuvants to the unbroken skin. This approach yields both antibody and T-cell responses, including priming of CD8 T cells (2-5). However, little is known about the capacity of EPI to prime memory CD8 T cells capable of protection against pathogen challenge, nor do we understand how adjuvants operate when applied to the intact skin.Several adjuvants can induce CD8 T-cell priming through EPI. These include toll-like receptor (TLR) agonists such as imiquimod and CpG (6-9), but also the ADP ribosylating bacterial exotoxins such as cholera toxin (CT) and the closely related Escherichia coli heat-labile enterotoxin (LT) (10-12). Application of such toxins to the skin is safe and effective in priming humoral and cellular responses in both mice and humans (4, 10, 13-15). However, previous studies failed to define which adjuvants afford optimal priming of CD8 T-cell responses and durable protective memory. Furthermore, whereas TLR pathways are well characterized, the basis for adjuvanticity of bacterial exotoxins remains mysterious.Here we compared multiple adjuvants for epicutaneous priming and found that CT was superior in effective induction of CD8 T-cell responses, resulting in protective immunity against pathogen challenge. We find that CT-mediated adjuvanticity occurs in the absence of typical TLR and inflammasome signaling pathways and that langerin-expressing cells (including Langerhans cells) are dispensable for EPI using CT. The adjuvant properties of CT were, however, dependent on host sensi...

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“…The potency of the vaccine was further augmented by the use of DC-activating adjuvants, notably ODN-CpG. Synthetic ODN-CpG mimics bacterial DNA and binds toll-like receptor (TLR)-9 providing a "danger signal" to activate the immune response [120]. Therefore, vaccination with a long peptide containing CD8 + CTL and CD4 + Th cell epitopes, and DC-activating agents could augment the immunity generated against peptide-based HPV vaccines [100].…”

Section: Vaccine Deliverymentioning

confidence: 99%

Advances in Peptide-based Human Papillomavirus Therapeutic Vaccines

Liu¹,

Hussein²,

Tóth³

et al. 2012

CTMC

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Cervical cancer is the second leading cause of cancer in women worldwide. Human papillomavirus (HPV) is responsible for all cases of cervical cancer. Commercial prophylactic HPV vaccines are now available, but unfortunately these vaccines have no therapeutic effect against established HPV infections. In order to accelerate the control of cervical cancer and treat established HPV infections, it is necessary to develop therapeutic vaccines to eradicate HPV by generating cell-mediated immunity against HPV infected cells. Two HPV-encoded early proteins, the E6 and E7 oncoproteins, are the preferred targets because they are consistently expressed in virtually all cervical cancer cells and are necessary for the induction and maintenance of HPV-associated disease. A variety of vaccine strategies have been employed targeting immune responses to these proteins. Peptide-based vaccines are a promising strategy for the development of therapeutic HPV vaccines because of their safety, stability, and ease of production. This review summarizes the prospects of peptidebased vaccines for the treatment of established HPV infections. We address the challenges that scientists currently face for developing peptide-based vaccines and explore feasible strategies for improving the potency of the induced immune response with the aim of treating established HPV infections.

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Transcutaneous Immunization with Cytotoxic T-Cell Peptide Epitopes Provides Effective Antitumor Immunity in Mice

Cited by 37 publications

References 17 publications

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination

Advances in Peptide-based Human Papillomavirus Therapeutic Vaccines

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