Vaccination With Human Papillomavirus Type 16 E7 Peptide With CpG Oligonucleotides for Prevention of Tumor Growth in Mice

Gendron, Kristin; Rodriguez, Alex; Sewell, David L.

doi:10.1001/archotol.132.3.327

Cited by 16 publications

(8 citation statements)

References 23 publications

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“…10,23,39 To the best of our knowledge, the presence of CpG ODN in subcutaneous immunization protocols such as ours uniformly has been reported to promote the T cell expansion. 16,40,41 Similarly, the presence of CpG ODN in intravenous or intraperitoneal immunization settings has been shown to induce CD8 T cell response. 17,42 In clinical studies, use of CpG ODN generates a strong peptide-specific CD81 T cell response.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical enhancement of CD8 T cell‐dependent anti‐tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine

Karan

Krieg

Lubaroff

2007

Intl Journal of Cancer

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Generation of antigen-specific CD81 T cell responses is considered optimal for an effective immunotherapy against cancer. In this study, we provide a proof of principle that in vitro observed diminished CD81 T cell response provided a strong in vivo tumor protection. Immunization with an adenovirus vaccine containing ovalbumin (OVA) gene (Ad5-OVA) strongly induces antigen-specific CD81 T cell responses measured in vitro using various immunological assays. However, in an attempt to augment the antigenic CD81 T cell response, coinjection of a TLR9 agonist CpG ODN with the viral vaccine unexpectedly reduced the CD81 T cell responses measured in vitro but provided a remarkably enhanced tumor protection compared to the CD81 T cell response generated by Ad5-OVA vaccine alone. Interestingly, despite reduced ex vivo/in vitro CD81 T cell responses following Ad5-OVA1CpG immunization, immunodepletion studies revealed that the augmented anti-tumor immunity was primarily dependent on CD81 T cells. The magnitude and effector function of anti-OVA CD81 T cells remain low following primary and secondary antigenic challenge, presenting a dichotomy between in vitro CD8 T cell responses and in vivo anti-tumor immunity. To examine the impact of CpG ODN, we observed that presence of CpG suppresses the CD81 T cell proliferation both in vitro and in vivo. These data demonstrate that coadministration of adenovirus vaccine with a TLR9 agonist can generate potentially effective tumorreactive CD81 T cells in vivo. In addition, the results indicate that widely used standard immune parameters may not predict the vaccine efficacy containing a TLR9 agonist as adjuvant. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Paradoxical enhancement of CD8 T cell‐dependent anti‐tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine

Karan

Krieg

Lubaroff

2007

Intl Journal of Cancer

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“…Given ISG15 adjuvant properties to enhance E7-specific-CTL responses that are essential to target established pre-existing HPV infections, 15,16 we investigated the role of ISG15-elicited CD8 T-cells for HPV-associated tumor elimination. Therefore, in a therapeutic setting, CD8 T-cells were depleted by intraperitoneally injection of anti-CD8 antibody, beginning 1-day before tumor inoculation and repeated every 3 days post-tumor implantation (Figure 6c).…”

Section: Isg15 Acted As An Effective Cd8 T-cell Immunoadjuvant Inducimentioning

confidence: 99%

Ubiquitin-like Molecule ISG15 Acts as an Immune Adjuvant to Enhance Antigen-specific CD8 T-cell Tumor Immunity

et al. 2015

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ISG15 is an ubiquitin-like protein induced by type I interferon associated with antiviral activity. ISG15 is also secreted and known to function as an immunomodulatory molecule. However, ISG15's role in influencing the adaptive CD8 T-cell responses has not been studied. Here, we demonstrate the efficacy of ISG15 as a vaccine adjuvant, inducing human papilloma virus (HPV) E7-specific IFNγ responses as well as the percentage of polyfunctional, cytolytic, and effector CD8 T-cell responses. Vaccination with ISG15 conferred remarkable control and/or regression of established HPV-associated tumor-bearing mice. T-cell depletion coupled with adoptive transfer experiments revealed that ISG15 protective efficacy was CD8 T-cell mediated. Importantly, we demonstrate that ISG15 vaccine-induced responses could be generated independent of ISGylation, suggesting that responses were mostly influenced by free ISG15. Our results provide more insight into the immunomodulatory properties of ISG15 and its potential to serve as an effective immune adjuvant in a therapeutic tumor or infectious disease setting.

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“…Nearly 40% of activated T cells were antigen specific within the BM. This percentage, achieved with only two weekly vaccinations, is much higher than the percentage of Ag-specific cells found in any other organ after peripheral vaccination with the same peptide [16]. This high percentage may be due to proliferation of antigen-specific T cells within the BM.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow vaccination: A novel approach to enhance antigen specific antitumor immunity

Fresnay

Zhang

Strome

et al. 2011

Vaccine

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Bone marrow (BM) serves as a reservoir for a unique population of memory T cells with strong effector properties that make them ideal target for cancer immunotherapy strategies. However, direct vaccination and priming of T cells within the BM of the host has never been investigated. This study evaluates the specific immune response induced via a new method of direct intra-bone marrow (IBM) vaccinations in an animal model of human papillomavirus-associated cancer. We found that IBM vaccinations with the class I HPV-16 E7 epitope induce large numbers of activated, IFN-γ-producing E7-specific lymphocytes in the BM. In prophylactic tumor challenge experiments, direct intra-BM vaccination was found to be protective against tumor formation for 80% of the mice. In the therapeutic setting, IBM vaccination induced tumor regression in 3 of 10 vaccinated mice and delayed tumor growth in the remaining animals. Finally, adoptive transfer of BM cells from IBM vaccinated mice to naïve animals conferred complete protection against tumor growth. These data demonstrate the capacity of direct IBM vaccination to induce potent antigen-specific immunity resulting in protection from tumor growth in an animal model. Specifically targeting BM T cells with vaccines may improve responses to cancer immunotherapy and offer important clinical advantages, especially in the setting of bone marrow malignancies.

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Vaccination With Human Papillomavirus Type 16 E7 Peptide With CpG Oligonucleotides for Prevention of Tumor Growth in Mice

Cited by 16 publications

References 23 publications

Paradoxical enhancement of CD8 T cell‐dependent anti‐tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine

Paradoxical enhancement of CD8 T cell‐dependent anti‐tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine

Ubiquitin-like Molecule ISG15 Acts as an Immune Adjuvant to Enhance Antigen-specific CD8 T-cell Tumor Immunity

Bone marrow vaccination: A novel approach to enhance antigen specific antitumor immunity

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