Recombinant DNA vaccines protect against tumors that are resistant to recombinant vaccinia vaccines containing the same gene

Ch, Chen; Wang, T-L.; H, Ji; Cc, Hung; Dm, Pardoll; Cheng, Wen-Fang; Ling, Morris; Wu, Tong

doi:10.1038/sj.gt.3301370

Cited by 22 publications

(9 citation statements)

References 35 publications

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“…We applied VICE to generate immune-resistant tumor cells in a human papillomavirus (HPV) type-16-associated cervical cancer model, TC-1, which allows us to accurately trace tumor-reactive CTLs based on specificity for the HPV antigen E7 (13). After 3 serial passages, we created TC-1 P3, a derivative of the parental TC-1 line (P0), that is completely impervious to Sig/E7/LAMP-1-based vaccination (19–21). …”

Section: Resultsmentioning

confidence: 99%

Cancer Vaccination Drives Nanog-Dependent Evolution of Tumor Cells toward an Immune-Resistant and Stem-like Phenotype

et al. 2012

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Due to the exquisite specificity and potency of the immune system, vaccination is in theory the most precise and powerful approach for controlling cancer. However, current data from clinical trials indicate that vaccination rarely yields significant benefits for cancer patients in terms of tumor progression and long-term survival. The poor clinical outcomes of vaccination are primarily caused by mechanisms of immune tolerance, especially within the tumor microenvironment. Here we report that vaccination drives the evolution of tumor cells towards an immune-resistant and stem-like phenotype that promotes tumor growth and nullifies the cytotoxic T lymphocyte (CTL) response. The emergence of this phenotype required the transcription factor Nanog, which is induced as a consequence of immune selection. Nanog expression enhanced the stem-like features of tumor cells and protected them from killing by tumor-reactive CTLs. Delivery of siNanog into tumor-bearing mice rendered the tumor vulnerable to immune surveillance and strongly suppressed its growth. Together, our findings demonstrate tumor adaptation to vaccination through gain of an immune-resistant, stem-like phenotype and identify Nanog as a central molecular target in this process. Future vaccination technology should consider Nanog an important target to enhance the immunotherapeutic response.

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Section: Resultsmentioning

confidence: 99%

Cancer Vaccination Drives Nanog-Dependent Evolution of Tumor Cells toward an Immune-Resistant and Stem-like Phenotype

et al. 2012

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“…It has also been shown that plasmid vaccines can protect against tumors that are resistant to recombinant vaccinia vaccines containing the same gene. 4 Furthermore, plasmid vaccines can be relatively easily and inexpensively produced and do not require the special handling or storage that some microbial vectors require.…”

mentioning

confidence: 99%

Phase I Study of a Plasmid DNA Vaccine Encoding MART-1 in Patients with Resected Melanoma at Risk for Relapse

Triozzi

Aldrich

Allen

et al. 2005

Journal of Immunotherapy

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Immunization with plasmid DNA represents an attractive method for increasing cellular immune responses against cancer antigens. The safety and immunologic response of a plasmid encoding the MART-1 melanocyte differentiation antigen was evaluated in 12 patients with resected melanoma at risk for relapse. As a control, patients were also administered a plasmid encoding hepatitis B surface antigen (HBsAg). After establishing immunologic activity of the vaccines in mice, groups of three to six HLA-A2-positive patients were enrolled into one of three cohorts in which they received intramuscular injections of the MART-1 plasmid into the right deltoid and the HBsAg plasmid into the left deltoid at doses of 0.1, 0.3, or 1.0 mg on days 1, 43, 85, and 127. Injections were well tolerated. Toxicity was limited to grade 1 pain and injection site tenderness. Systemic toxicity was not observed. Although baseline MART-1-specific lymphoproliferative and ELISPOT responses were evident, no patient manifested increases after injection of the MART-1 plasmid. Furthermore, changes in MART-1-specific precursors were not evident after immunization as assessed by an in vitro stimulation assay. No patients manifested a lymphoproliferative response to HBsAg antigen, and significant antibody responses to HBsAg were also not observed. Although injections were safe, the authors could not show significant immunologic responses to plasmid encoding MART-1 or HBsAg using the dose, schedule, and route of administration applied. This study underscores species differences in the ability to respond to plasmid immunogens.

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“…The outcome of E7-directed human clinical trials using peptide 11 or recombinant vaccinia viruses expressing E7 and E6 12 as immunogens has been equivocal, although CTL generation was observed in some patients. Although a number of experimental therapeutic vaccines for HPV-associated malignancy has been reported in animal models, (for example, Chu et al, 9 Peng et al, 13 Herd et al, 14 Echchannaoui et al, 15 Daftarian et al, 16 Chen et al 17 ), it is clear that potent strategies readily applicable to humans for inducing CTLs and for priming and boosting anti-tumor responses are necessary, and yet to be developed.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B surface antigen fusions delivered by DNA vaccination elicit CTL responses to human papillomavirus oncoproteins associated with tumor protection

et al. 2010

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We describe the construction and evaluation of a recombinant hepatitis B surface antigen (HBsAg)-vectored DNA vaccine encoding the E7 and E6 tumor-associated oncoproteins of human papillomavirus (HPV) type 16. We show the induction of effector and memory cytotoxic T lymphocyte responses to E7 and E6 class I-restricted epitopes after a single immunization, which were associated with tumor prevention and therapy. The findings vindicate the use of a HBsAg-based DNA vaccine as a vehicle to elicit responses to co-encoded tumor antigens, and have specific implications for the development of a therapeutic vaccine for HPV-associated squamous carcinomas.

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Recombinant DNA vaccines protect against tumors that are resistant to recombinant vaccinia vaccines containing the same gene

Cited by 22 publications

References 35 publications

Cancer Vaccination Drives Nanog-Dependent Evolution of Tumor Cells toward an Immune-Resistant and Stem-like Phenotype

Cancer Vaccination Drives Nanog-Dependent Evolution of Tumor Cells toward an Immune-Resistant and Stem-like Phenotype

Phase I Study of a Plasmid DNA Vaccine Encoding MART-1 in Patients with Resected Melanoma at Risk for Relapse

Hepatitis B surface antigen fusions delivered by DNA vaccination elicit CTL responses to human papillomavirus oncoproteins associated with tumor protection

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