Preventive DNA vaccination against CEA-expressing tumors with anti-idiotypic scFv6.C4 DNA in CEA-expressing transgenic mice

Denapoli, Priscila Martins Andrade; Zanetti, Bianca Ferrarini; Santos, A. A. dos; Moraes, Jane Zveiter de; Han, Sang Won

doi:10.1007/s00262-016-1940-4

Cited by 10 publications

(9 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…C57BL/6 mice were subcutaneously injected with several concentrations of B16F10 cells. In contrast with the rapid tumor development in mice from the group injected with a optimal number of 1 × 10 5 cells per mouse established by previous studies [ 41 , 42 ], inoculation of mice with lower numbers of cells postponed the onset of tumor formation, with variable growth kinetics, as evidenced by the dispersion of growth curves (Fig. 1 a).…”

Section: Resultscontrasting

confidence: 80%

Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform for early detection of cancer

Yin

Jiang²,

Shen

et al. 2022

J Transl Med

View full text Add to dashboard Cite

Background Cancer screening provides the opportunity to detect cancer early, ideally before symptom onset and metastasis, and offers an increased opportunity for a better prognosis. The ideal biomarkers for cancer screening should discriminate individuals who have not developed invasive cancer yet but are destined to do so from healthy subjects. However, most cancers lack effective screening recommendations. Therefore, further studies on novel screening strategies are urgently required. Methods We used a simple suboptimal inoculation melanoma mouse model to obtain ‘pre-diagnostic samples’ of mice with macroscopic melanomas. High-throughput sequencing and bioinformatic analysis were employed to identify differentially expressed RNAs in platelet signatures of mice injected with a suboptimal number of melanoma cells (eDEGs) compared with mice with macroscopic melanomas and negative controls. Moreover, 36 genes selected from the eDEGs via bioinformatics analysis were verified in a mouse validation cohort via quantitative real-time PCR. LASSO regression was utilized to generate the prediction models with gene expression signatures as the best predictors for occult tumor progression in mice. Results These RNAs identified from eDEGs of mice injected with a suboptimal number of cancer cells were strongly enriched in pathways related to immune response and regulation. The prediction models generated by 36 gene qPCR verification data showed great diagnostic efficacy and predictive value in our murine validation cohort, and could discriminate mice with occult tumors from control group (area under curve (AUC) of 0.935 (training data) and 0.912 (testing data)) (gene signature including Cd19, Cdkn1a, S100a9, Tap1, and Tnfrsf1b) and also from macroscopic tumor group (AUC of 0.920 (training data) and 0.936 (testing data)) (gene signature including Ccr7, Cd4, Kmt2d, and Ly6e). Conclusions Our proof-of-concept study provides evidence for potential clinical relevance of blood platelets as a platform for liquid biopsy-based early detection of cancer.

show abstract

Section: Resultscontrasting

confidence: 80%

Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform for early detection of cancer

Yin

Jiang²,

Shen

et al. 2022

J Transl Med

View full text Add to dashboard Cite

show abstract

“…C57BL/6 mice were subcutaneously injected with several concentrations of B16F10 cells. In contrast with the rapid tumor development in mice from the group injected with a optimal number of 1 × 10 5 cells per mouse established by previous studies 14,15 , inoculation of mice with lower numbers of cells postponed the onset of tumor formation, with variable growth kinetics, as evidenced by the dispersion of growth curves (Fig. 1a).…”

Section: Main Textcontrasting

confidence: 79%

Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform of cancer screening for early detection of cancer

Yin

Jiang²,

et al. 2021

Preprint

View full text Add to dashboard Cite

Cancer screening provides the opportunity to detect cancer early, ideally before symptom onset and metastasis, and offers an increased opportunity for a better prognosis. The ideal biomarkers for cancer screening should discriminate individuals who have not developed invasive cancer yet but are destined to do so from healthy subjects. However, most cancers lack effective screening recommendations. Therefore, further studies on novel screening strategies are urgently required. Here, our proof-of-concept study shows blood platelets could be a platform for liquid biopsy-based early cancer detection. By using a simple suboptimal inoculation melanoma mouse model, we identified differentially expressed RNAs in platelet signatures of mice injected with a suboptimal number of cancer cells (eDEGs) compared with mice with macroscopic melanomas and negative controls. These RNAs were strongly enriched in pathways related to immune response and regulation. Moreover, 36 genes selected from the eDEGs via bioinformatics analyses were verified in a mouse validation cohort via quantitative real-time PCR. LASSO regression was employed to generate the prediction models with gene expression signatures as the best predictors for occult tumor progression in mice. The prediction models showed great diagnostic efficacy and predictive value in our murine validation cohort, and could discriminate mice with occult tumors from control group (area under curve (AUC) of 0.935 (training data) and 0.912 (testing data)) (gene signature including Cd19, Cdkn1a, S100a9, Tap1, and Tnfrsf1b) and also from macroscopic tumor group (AUC of 0.920 (training data) and 0.936 (testing data)) (gene signature including Ccr7, Cd4, Kmt2d, and Ly6e). Our study provides evidence for potential clinical relevance of blood platelets as a platform for liquid biopsy-based early detection of cancer. Furthermore, the eDEGs are mostly immune-related, not tumor-specific. Hence it is possible platelets-based liquid biopsy could enable simultaneous early detection of cancers from multiple organs of origin. It is also feasible to determine the origin of cancer since platelet profiles are influenced by tumor type.

show abstract

“…Over the past years, anti-idiotypic antibodies have been studied and used in a variety of situations including attempts to use them as therapeutic agents (Denapoli et al, 2017). They are ideal for bioanalytical assays in preclinical research and clinical drug monitoring due to their high specificity and sensitivity (Bulashev et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection

Wang

Yang

Huang

et al. 2017

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody dependent enhancement (ADE). Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM) of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2) and DENV-2 prM monoclonal antibody (prM mAb) could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs) specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo, interferon-α and γ receptor-deficient mice (AG6) were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10) and alaninea minotransferase (ALT) in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo, suggested that anti-idiotypic antibodies might be a new choice to be considered to treat DENV infection.

show abstract

Preventive DNA vaccination against CEA-expressing tumors with anti-idiotypic scFv6.C4 DNA in CEA-expressing transgenic mice

Cited by 10 publications

References 30 publications

Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform for early detection of cancer

Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform for early detection of cancer

Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform of cancer screening for early detection of cancer

Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection

Contact Info

Product

Resources

About