HER2/neu DNA vaccination by intradermal gene delivery in a mouse tumor model: Gene gun is superior to jet injector in inducing CTL responses and protective immunity.

Abstract:

:DNA vaccines are potential tools for the induction of immune responses against both infectious disease and cancer. The dermal application of DNA vaccines is of particular interest since the epidermal and dermal layers of the skin are characterized by an abundance of antigen-presenting cells (APCs). The aim of our study was to compare tumor protection as obtained by two different methods of intradermal DNA delivery (gene gun and jet injector) in a well-established HER2/neu mouse tumor model. BALB/c mice were immunized twice with a HER2/neu-coding plasmid by gene gun or jet injector. Mice were then subcutaneously challenged with HER2/neu(+) syngeneic D2F2/E2 tumor cells. Protection against subsequent challenges with tumor cells as well as humoral and T-cell immune responses induced by the vaccine were monitored. Gene gun immunization was far superior to jet injector both in terms of tumor protection and induction of HER2/neu-specific immune responses. After gene gun immunization, 60% of the mice remained tumor-free until day 140 as compared with 25% after jet injector immunization. Furthermore, gene gun vaccination was able to induce both a strong T(H)1-polarized T-cell response with detectable cytotoxic T-lymphocyte (CTL) activity and a humoral immune response against HER2/neu, whereas the jet injector was not. Although the disadvantages that were associated with the use of the jet injector in our model may be overcome with methodological modifications and/or in larger animals, which exhibit a thicker skin and/or subcutaneous muscle tissue, we conclude that gene gun delivery constitutes the method of choice for intradermal DNA delivery in preclinical mouse models and possibly also for the clinical development of DNA-based vaccines.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Nguyen-Hoai T,Kobelt D,Hohn O,Vu MD,Schlag PM,Dörken B,Norley S,Lipp M,Walther W,Pezzutto A,Westermann J

doi

10.4161/onci.22563

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

1537-1545

issue

9

eissn

2162-4011

issn

2162-402X

pii

2012ONCOIMM0245R

journal_volume

1

pub_type

杂志文章
  • FIST, a sword and shield fusokine for cancer immunotherapy.

    abstract::To antagonize tumor-derived TGFβ contemporaneously to anticancer immunotherapy, we genetically engineered a fusion protein coupling IL-2 and the ectodomain of TGFβ receptor II (Fusion of Interleukin-2 and Soluble TGFβ receptor - a.k.a. FIST). FIST possesses intriguing gain-of-function properties and induces potent act...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.1.2.18458

    authors: Penafuerte C,Galipeau J

    更新日期:2012-03-01 00:00:00

  • Poly(I:C) primes primary human glioblastoma cells for an immune response invigorated by PD-L1 blockade.

    abstract::Prognosis of glioblastoma remains dismal, underscoring the need for novel therapies. Immunotherapy is generating promising results, but requires combination strategies to unlock its full potential. We investigated the immunomodulatory capacities of poly(I:C) on primary human glioblastoma cells and its combinatorial po...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1407899

    authors: De Waele J,Marcq E,Van Audenaerde JR,Van Loenhout J,Deben C,Zwaenepoel K,Van de Kelft E,Van der Planken D,Menovsky T,Van den Bergh JM,Willemen Y,Pauwels P,Berneman ZN,Lardon F,Peeters M,Wouters A,Smits EL

    更新日期:2017-12-12 00:00:00

  • A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes.

    abstract::The tumor microenvironment is characterized by of high levels of extracellular nucleotides that are metabolized through the dynamic and sequential action of cell surface enzymes (ectoenzymes). These ectoenzymes operate according to their spatial arrangement, as part of (1) continuous (molecules on the same cell) or (2...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.26246

    authors: Horenstein AL,Chillemi A,Zaccarello G,Bruzzone S,Quarona V,Zito A,Serra S,Malavasi F

    更新日期:2013-09-01 00:00:00

  • Chronic activation of DNA damage signals causes tumor immune evasion in the chemoresistant niche.

    abstract::DNA damage responses have been proposed as a gatekeeper to block tumorigenesis. We identify unexpected mechanisms whereby ATM-mediated pathway interacts with NFκB inflammatory cascades, leading to upregulation of integrin-αbβ3 on chemoresistant tumor cells. The integrin-αbβ3 is responsible for impeding tumor-specific ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19123

    authors: Jinushi M

    更新日期:2012-05-01 00:00:00

  • Novel treatment strategy with autologous activated and expanded natural killer cells plus anti-myeloma drugs for multiple myeloma.

    abstract::This proof-of-concept single-arm open-label phase I clinical trial (NCT02481934) studied the safety and efficacy of multiple infusions of activated and expanded natural killer (NKAE) cells in combination with anti-myeloma drugs in multiple myeloma patients. It included five patients with relapsed or refractory MM who ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1250051

    authors: Leivas A,Perez-Martinez A,Blanchard MJ,Martín-Clavero E,Fernández L,Lahuerta JJ,Martinez-Lopez J

    更新日期:2016-11-22 00:00:00

  • Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma.

    abstract::Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.965570

    authors: Partlová S,Bouček J,Kloudová K,Lukešová E,Zábrodský M,Grega M,Fučíková J,Truxová I,Tachezy R,Špíšek R,Fialová A

    更新日期:2015-01-30 00:00:00

  • The pancreatic cancer microenvironment: an immunologic battleground.

    abstract::Recent studies of human pancreatic cancer challenge the mouse model-derived notion that the pancreas is a site of immune privilege. A heavy infiltration of CD8+ T cells expressing programmed cell death 1 (PD-1) and smaller numbers of myeloid cells and regulatory T cells provides rationale for the clinical evaluation o...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.950171

    authors: Pillarisetty VG

    更新日期:2014-08-03 00:00:00

  • Oncolytic virotherapy with an armed vaccinia virus in an orthotopic model of renal carcinoma is associated with modification of the tumor microenvironment.

    abstract::Oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. We have constructed a vaccinia virus (WR strain) deleted for thymidine kinase (TK) and ribonucleotide reductase (RR) genes that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil ph...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1080414

    authors: Fend L,Remy-Ziller C,Foloppe J,Kempf J,Cochin S,Barraud L,Accart N,Erbs P,Fournel S,Préville X

    更新日期:2015-10-06 00:00:00

  • Immunosurveillance in esophageal carcinoma: The decisive impact of regulatory T cells.

    abstract::Neoadjuvant radiochemotherapy of esophageal carcinomas causes a variable degree of depletion of tumor-infiltrating FOXP3+ regulatory T cells (Tregs). The frequency of local Tregs in the operative specimens negatively correlates with the pathological response and overall patient survival. These results underscore the i...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1064581

    authors: Vacchelli E,Semeraro M,Adam J,Dartigues P,Zitvogel L,Kroemer G

    更新日期:2015-07-01 00:00:00

  • Inhibition of formyl peptide receptor 1 reduces the efficacy of anticancer chemotherapy against carcinogen-induced breast cancer.

    abstract::The loss-of-function mutation of formyl peptide receptor 1 (FPR1) has a negative impact on the progression-free and overall survival of breast cancer patients treated with anthracycline-based adjuvant chemotherapy. This effect may be attributed to the fact that chemotherapy-induced antitumor immunity requires FPR1 and...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1139275

    authors: Baracco EE,Pietrocola F,Buqué A,Bloy N,Senovilla L,Zitvogel L,Vacchelli E,Kroemer G

    更新日期:2016-02-18 00:00:00

  • A novel immunization strategy using cytokine/chemokines induces new effective systemic immune responses, and frequent complete regressions of human metastatic melanoma.

    abstract::Immune responses have been elicited by a variety of cancer vaccines, but seldom induce regressions of established cancers in humans. As a novel therapeutic immunization strategy, we tested the hypothesis that multiple cytokines/chemokines secreted early in secondary responses ex-vivo might mimic the secretory environm...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1386827

    authors: Valentine FT,Golomb FM,Harris M,Roses DF

    更新日期:2017-10-30 00:00:00

  • Co-delivery of the NKT agonist α-galactosylceramide and tumor antigens to cross-priming dendritic cells breaks tolerance to self-antigens and promotes antitumor responses.

    abstract::Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8+ T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT ce...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1339855

    authors: Ghinnagow R,De Meester J,Cruz LJ,Aspord C,Corgnac S,Macho-Fernandez E,Soulard D,Fontaine J,Chaperot L,Charles J,Soncin F,Mami-Chouaib F,Plumas J,Faveeuw C,Trottein F

    更新日期:2017-08-18 00:00:00

  • Induction of immunogenic cell death by targeting RIG-I-like helicases in pancreatic cancer.

    abstract::RIG-I-like helicases (RLH) are cytosolic sensors for viral RNA inducing type I interferon production. We found that pancreatic cancer cells express functional RLH and are susceptible to RLH-induced apoptosis via intrinsic and extrinsic pathways. Tumor cells displayed features of immunogenic cell death resulting in den...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.955687

    authors: Schnurr M,Duewell P

    更新日期:2014-12-13 00:00:00

  • Deubiquitinases A20 and CYLD modulate costimulatory signaling via CD137 (4-1BB).

    abstract::TRAF2 dependent K63-polyubiquitinations have been recently shown to connect CD137 (4-1BB) stimulation to NF-κB activation. In a search of deubiquitinase enzymes (DUBs) that could regulate such a signaling route, A20 and CYLD were found to coimmunoprecipitate with CD137 and TRAF2 complexes. Indeed, overexpression of A2...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1368605

    authors: Azpilikueta A,Bolaños E,Lang V,Labiano S,Aznar MA,Etxeberria I,Teijeira A,Rodriguez-Ruiz ME,Perez-Gracia JL,Jure-Kunkel M,Zapata JM,Rodriguez MS,Melero I

    更新日期:2017-09-21 00:00:00

  • A perspective on new immune adjuvant principles: Reprogramming inflammatory states to permit clearance of cancer cells and other age-associated cellular pathologies.

    abstract::Aging entails the accumulation of neoantigens comprised of aggregated, oxidized, mutated and misfolded biomolecules, including advanced-glycation end projects (AGEs). There is evidence that the immune system can recognize and clear cells fouled by these molecular debris, which contribute to the emergence of cancer and...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21358

    authors: Prendergast GC,Metz R

    更新日期:2012-09-01 00:00:00

  • High sensitivity of cancer exome-based CD8 T cell neo-antigen identification.

    abstract::Recent data suggest that T-cell reactivity against tumor-specific neo-antigens may be central to the clinical efficacy of cancer immunotherapy. The development of personalized vaccines designed to boost T-cell reactivity against patient specific neo-antigens has been proposed largely on the basis of these findings. Wo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.28836

    authors: van Buuren MM,Calis JJ,Schumacher TN

    更新日期:2014-05-14 00:00:00

  • Interleukin-17A promotes the growth of human germinal center derived non-Hodgkin B cell lymphoma.

    abstract::Interleukin (IL)-17A belongs to IL-17 superfamily and binds the heterodimeric IL-17 receptor (R)(IL-17RA/IL-17RC). IL-17A promotes germinal center (GC) formation in mouse models of autoimmune or infectious diseases, but the role of IL-17A/IL-17AR complex in human neoplastic GC is unknown. In this study, we investigate...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1030560

    authors: Ferretti E,Di Carlo E,Ognio E,Guarnotta C,Bertoni F,Corcione A,Prigione I,Fraternali-Orcioni G,Ribatti D,Ravetti JL,Ponzoni M,Tripodo C,Pistoia V

    更新日期:2015-06-19 00:00:00

  • TLR2 ligation protects effector T cells from regulatory T-cell mediated suppression and repolarizes T helper responses following MVA-based cancer immunotherapy.

    abstract::Cancer immunotherapy is hampered by the immunosuppression maintained by regulatory T cells (Tregs) in tumor-bearing hosts. Stimulation of the Toll-like receptor 2 (TLR2) by Pam3Cys is known to affect Treg-mediated suppression. We found that Pam3Cys increases the proliferation of both CD4(+) effector T cells (Teffs) an...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21479

    authors: Amiset L,Fend L,Gatard-Scheikl T,Rittner K,Duong V,Rooke R,Muller S,Bonnefoy JY,Préville X,Haegel H

    更新日期:2012-11-01 00:00:00

  • A single centre phase II trial to assess the immunological activity of TroVax® plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma - the SKOPOS trial.

    abstract::Vaccines in combination with chemotherapy have been shown to be safe in different tumor types. We investigated the immunological activity of the TroVax® vaccine in combination with pemetrexed-cisplatin chemotherapy in malignant pleural mesothelioma (MPM). In this first line, open-label, single-arm, phase 2 study, pati...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1457597

    authors: Lester JF,Casbard AC,Al-Taei S,Harrop R,Katona L,Attanoos RL,Tabi Z,Griffiths GO

    更新日期:2018-09-07 00:00:00

  • Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-Seq.

    abstract::Recent studies have proposed that tumor-specific tumor-infiltrating CD8+ T lymphocytes (CD8 TIL) can be classified into two main groups: "exhausted" TILs, characterized by high expression of the inhibitory receptors PD-1 and TIM-3 and lack of transcription factor 1 (Tcf1); and "memory-like" TILs, with self-renewal cap...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1737369

    authors: Carmona SJ,Siddiqui I,Bilous M,Held W,Gfeller D

    更新日期:2020-03-12 00:00:00

  • Evaluation of innate and adaptive immunity contributing to the antitumor effects of PD1 blockade in an orthotopic murine model of pancreatic cancer.

    abstract::Despite the clinical success of anti-PD1 antibody (α-PD1) therapy, the immune mechanisms contributing to the antineoplastic response remain unclear. Here, we describe novel aspects of the immune response involved in α-PD1-induced antitumor effects using an orthotopic Kras (G12D)/p53(R172H)/Pdx1-Cre (KPC) model of panc...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1160184

    authors: D'Alincourt Salazar M,Manuel ER,Tsai W,D'Apuzzo M,Goldstein L,Blazar BR,Diamond DJ

    更新日期:2016-03-16 00:00:00

  • Tumor vascularity in ovarian cancer: T cells need breathing room.

    abstract::Tumor-infiltrating lymphocytes (TILs) are crucial for effective antitumor responses. However, hypoxia can skew T-cell differentiation and function, thereby perturbing TILs. We have demonstrated that TILs and their immune function are associated with tumor vascularization. These features are prognostic for improved dis...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.28272

    authors: Neilson D,MacPherson S,Townsend KN,Lum JJ

    更新日期:2014-04-08 00:00:00

  • A pipeline for identification and validation of tumor-specific antigens in a mouse model of metastatic breast cancer.

    abstract::Cancer immunotherapy continues to make headway as a treatment for advanced stage tumors, revealing an urgent need to understand the fundamentals of anti-tumor immune responses. Noteworthy is a scarcity of data pertaining to the breadth and specificity of tumor-specific T cell responses in metastatic breast cancer. Aut...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1685300

    authors: DeVette CI,Gundlapalli H,Lai SA,McMurtrey CP,Hoover AR,Gurung HR,Chen WR,Welm AL,Hildebrand WH

    更新日期:2019-11-29 00:00:00

  • Bendamustine with total body irradiation conditioning yields tolerant T-cells while preserving T-cell-dependent graft-versus-leukemia.

    abstract::Graft-versus-host disease (GvHD) remains a significant impediment to allogeneic hematopoietic cell transplantation (HCT) success, necessitating studies focused on alleviating GvHD, while preserving the graft-versus-leukemia (GvL) effect. Based on our previous studies showing bendamustine with total body irradiation (B...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1758011

    authors: Stokes J,Hoffman EA,Molina MS,Kummet N,Simpson RJ,Zeng Y,Katsanis E

    更新日期:2020-04-30 00:00:00

  • Differential Regulation of T-cell mediated anti-tumor memory and cross-protection against the same tumor in lungs versus skin.

    abstract::A major advantage of immunotherapy of cancer is that effector cells induced at one site should be able to kill metastatic cancer cells in other sites or tissues. However, different tissues have unique immune components, and very little is known about whether effector T cells induced against tumors in one tissue can wo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1439305

    authors: O'Konek JJ,Ambrosino E,Bloom AC,Pasquet L,Massilamany C,Xia Z,Terabe M,Berzofsky JA

    更新日期:2018-04-09 00:00:00

  • Trial watch: Dendritic cell-based interventions for cancer therapy.

    abstract::Dendritic cells (DCs) occupy a privileged position at the interface between innate and adaptive immunity, orchestrating a large panel of responses to both physiological and pathological cues. In particular, whereas the presentation of antigens by immature DCs generally results in the development of immunological toler...

    journal_title:Oncoimmunology

    pub_type: 评审

    doi:10.4161/onci.25771

    authors: Vacchelli E,Vitale I,Eggermont A,Fridman WH,Fučíková J,Cremer I,Galon J,Tartour E,Zitvogel L,Kroemer G,Galluzzi L

    更新日期:2013-10-01 00:00:00

  • LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma.

    abstract::Immunotherapy with immune checkpoint molecule-specific monoclonal antibody have obtained encouraging results from preclinical studies and clinical trials, which promoted us to explore whether this kind of immunotherapy could be applicable to head and neck squamous cell carcinoma (HNSCC). Lymphocyte activation gene-3 (...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1239005

    authors: Deng WW,Mao L,Yu GT,Bu LL,Ma SR,Liu B,Gutkind JS,Kulkarni AB,Zhang WF,Sun ZJ

    更新日期:2016-10-07 00:00:00

  • Procarcinogenic regulatory T cells in microbial-induced colon cancer.

    abstract::Regulatory T cell (Treg) promote IL-17-mediated colon tumorigenesis in multiple intestinal neoplasia (Min) mice colonized with enterotoxigenic Bacteroides fragilis (ETBF). Although they retain their immunosuppressive function, mucosal Treg are instrumental to initiate ETBF-triggered IL-17 colitis by limiting the avail...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1118601

    authors: Geis AL,Housseau F

    更新日期:2015-12-21 00:00:00

  • PD-1 checkpoint blockade in advanced melanoma patients: NK cells, monocytic subsets and host PD-L1 expression as predictive biomarker candidates.

    abstract::Blockade of the PD-1 receptor has revolutionized the treatment of metastatic melanoma, with significant increases in overall survival (OS) and a dramatic improvement in patient quality of life. Despite the success of this approach, the number of benefitting patients is limited and there is a need for predictive biomar...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1786888

    authors: Pico de Coaña Y,Wolodarski M,van der Haar Àvila I,Nakajima T,Rentouli S,Lundqvist A,Masucci G,Hansson J,Kiessling R

    更新日期:2020-08-28 00:00:00

  • Overcoming immunosuppression to enhance a p53MVA vaccine.

    abstract::A Phase I trial of a p53-targeting modified vaccinia Ankara (p53MVA) vaccine in patients afflicted with refractory gastrointestinal cancers demonstrated enhanced T-cell recognition of p53 following vaccination. However, this effect was transient suggesting that p53MVA requires combination with immunomodulatory agents ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.958949

    authors: Hardwick N,Chung V,Cristea M,Ellenhorn JD,Diamond DJ

    更新日期:2014-12-15 00:00:00