Th1 epitope selection for clinically effective cancer vaccines

Disis, Mary L.; Watt, W. C.; Cecil, Denise L.

doi:10.4161/21624011.2014.954971

Cited by 8 publications

(4 citation statements)

References 9 publications

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“…Pompei et al demonstrated that patients with known allergy had increased response to cancer therapy and cure rates compared with patients without allergy. This finding suggests that the helper T-cell subtype 2 (T H 2) hyperreactivity in allergic patients may have a role in cancer cell identification and clearance, challenging the belief that cancer clearance is a mainly T H 1-driven response . IgE levels may be associated with antitumor activity in patients with atopy (ie, patients with diagnoses of any of the triad of asthma, AD, or allergic rhinitis).…”

Section: Discussionmentioning

confidence: 99%

Noncutaneous and Cutaneous Cancer Risk in Patients With Atopic Dermatitis

et al. 2020

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IMPORTANCE Impaired skin barrier and aberrant immune function in atopic dermatitis (AD) may alter immune response to malignant cancer. Conflicting data exist on the risk of cancer in patients with AD.OBJECTIVE To assess the risk of noncutaneous and cutaneous cancers in patients with AD compared with the general population without AD. DATA SOURCES Studies identified from searches of MEDLINE and Embase that were published from 1946 and 1980, respectively, to January 3, 2019. The following search terms were used: [(exp NEOPLASMS/ OR neoplas*.tw. OR tumo*.tw. OR cancer*.tw. OR malignanc*.tw.) AND (exp Dermatitis, Atopic/ OR (atopic adj1 (dermatit* or neurodermatit*)).tw. OR eczema.tw. OR disseminated OR neurodermatit*.tw.)]. STUDY SELECTION Included were observational studies (cohort and case-control designs) reporting a risk estimate for cancer in patients with AD compared with a control group (general population or patients without AD).DATA EXTRACTION AND SYNTHESIS Two independent reviewers extracted data and assessed the risk of bias using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) assessment tool, modified for observational exposure studies. Data were pooled using a random-effects model and expressed as standardized incidence ratios (SIRs) or odds ratios (ORs) with 95% CIs. Heterogeneity was assessed using the Cochrane Q statistic and the I 2 statistic. MAIN OUTCOMES AND MEASURESThe main outcome of the study was risk of cancer measured by SIRs or ORs. RESULTSThis systematic review and meta-analysis included 8 population-based cohort studies (n = 5 726 692 participants) and 48 case-control studies (n = 114 136 participants). Among cohort studies, a statistically significant association was found between AD and keratinocyte carcinoma (5 studies; pooled SIR, 1.46; 95% CI, 1.20-1.77) as well as cancers of the kidney (2 studies; pooled SIR, 1.86; 95% CI, 1.14-3.04), central nervous system (2 studies; pooled SIR, 1.81; 95% CI, 1.22-2.70), and pancreas (1 study; SIR, 1.90; 95% CI, 1.03-3.50). Among 48 case-control studies, pooled effects showed patients with AD had statistically significantly lower odds of central nervous system cancers (15 studies; pooled OR, 0.76; 95% CI, 0.70-0.82) and pancreatic cancer (5 studies; pooled OR, 0.81; 95% CI, 0.66-0.98), contrary to the higher incidence found in cohort studies. Case-control studies also demonstrated lower odds of lung and respiratory system cancers (4 studies; pooled OR, 0.61; 95% CI, 0.45-0.82). No evidence of association was found between AD and other cancer types, including melanoma. There was substantial heterogeneity between studies for many other cancers, which precluded pooling of data, and there was moderate to serious risk of bias among included studies. CONCLUSIONS AND RELEVANCEObservational evidence suggests potential associations between AD and increased risk of keratinocyte carcinoma and kidney cancer as well as lower odds of lung and respiratory system cancers. Further research is needed to address the heterogeneity and limitatio...

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Section: Discussionmentioning

confidence: 99%

Noncutaneous and Cutaneous Cancer Risk in Patients With Atopic Dermatitis

et al. 2020

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“…In summary, targeting an endogenous RNA adjuvant activity in vaccine recipients by antigens expressing well-defined cationic domains may help to design new generations of DNA vaccines that efficiently prime Th1-biased antibody and T-cell responses against chronic virus infections or tumours 52 , 53 .…”

Section: Discussionmentioning

confidence: 99%

Cationic domains in particle-forming and assembly-deficient HBV core antigens capture mammalian RNA that stimulates Th1-biased antibody responses by DNA vaccination

Krieger

Stifter

Riedl

et al. 2018

Sci Rep

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The HBV core protein self-assembles into particles and encapsidates immune-stimulatory bacterial RNA through a cationic COOH-terminal (C150–183) domain. To investigate if different cationic domains have an impact on the endogenous RNA-binding of HBV-C antigens in mammalian cells, we developed a strep-tag (st) based expression/purification system for HBV-C/RNA antigens in vector-transfected HEK-293 cells. We showed that HBV-stC but not HBV-stC149 particles (lacking the cationic domain) capture low amounts of mammalian RNA. Prevention of specific phosphorylation in cationic domains, either by exchanging the serine residues S155, S162 and S170 with alanines (HBV-stCAAA) or by exchanging the entire cationic domain with a HIV-tat48–57-like sequence (HBV-stC149tat) enhanced the encapsidation of RNA into mutant core particles. Particle-bound mammalian RNA functioned as TLR-7 ligand and induced a Th1-biased humoral immunity in B6 but not in TLR-7−/− mice by exogenous (protein) and endogenous (DNA) vaccines. Compared to core particles, binding of mammalian RNA to freely exposed cationic domains in assembly-deficient antigens was enhanced. However, RNA bound to non-particulate antigens unleash its Th1-stimulating adjuvant activity by DNA- but not protein-based vaccination. Mammalian RNAs targeted by an endogenously expressed antigen thus function as a natural adjuvant in the host that facilitates priming of Th1-biased immune responses by DNA-based immunization.

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“…The balance of T cell responses between CD8 C cytotoxic T cells (CTL), CD4 C Th1, Th2, Th9, Th17 or Treg induced against HPV antigens included in the vaccine might have been unfit to trigger a clinical response. 28,29 In addition, induction of the recently described genital tissue resident memory T cells (Trm) may be critical for highly effective vaccines against HPV infections and their associated cancers. 30 The modulation of the local immune environment by HPV infected or transformed cells might have prevented T cells to effectively clear lesions.…”

Section: Clinical Evaluation Of Immunotherapeutic Interventions Againmentioning

confidence: 99%

Moving forward with human papillomavirus immunotherapies

Çuburu

Schiller

2016

Human Vaccines & Immunotherapeutics

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Persistent human papillomavirus (HPV) is the primary etiologic agent of cervical cancer and causes a significant number of vulvar, penile, anal and oropharyngeal cancers. The development of highly effective HPV therapeutic vaccines is a reasonable goal given the recent advances in basic and applied immunology. A number of vaccine strategies designed to induce systemic T cell responses have been tested in clinical trials against high grade cervical or vulvar high grade neoplasia and cancers, but with limited success. In line with the emerging trend to focus more on the epithelial context of HPV infection and premalignant disease, it might be advantageous to develop vaccination strategies that promote trafficking of HPV-specific T cells into lesions and overcome the local immunosuppressive environment. The development of more biologically relevant animal models would improve the preclinical evaluation of therapeutic vaccine candidates. Finally, persistent infection and low grade lesions may prove to be easier targets for therapeutic vaccines, and these vaccines would likely be commercially viable in high income countries and valuable components in screen and treat programs in low resource settings.

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Th1 epitope selection for clinically effective cancer vaccines

Cited by 8 publications

References 9 publications

Noncutaneous and Cutaneous Cancer Risk in Patients With Atopic Dermatitis

Noncutaneous and Cutaneous Cancer Risk in Patients With Atopic Dermatitis

Cationic domains in particle-forming and assembly-deficient HBV core antigens capture mammalian RNA that stimulates Th1-biased antibody responses by DNA vaccination

Moving forward with human papillomavirus immunotherapies

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