Induction of cytotoxic T lymphocytes in mice against the principal neutralizing domain of HIV-1 by immunization with an engineered T-cytotoxic-T-helper synthetic peptide construct

Lasarte, Juan José; Sarobe, Pablo; Gullón, Arturo; Prìeto, Jesús; Borrás‐Cuesta, Francisco

doi:10.1016/0008-8749(92)90140-k

Cited by 40 publications

(24 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD4 ϩ Th cells play an important role on the induction of CTL (23,(31)(32)(33)(34). However, it has also been described that depletion of CD4 ϩ T cells may favor the induction of CTL responses (14,22,35), and enhance the therapeutic efficacy in tumor rejection (14,35) suggesting that CD4 ϩ T cells play a regulatory role.…”

Section: Discussionmentioning

confidence: 99%

“…Also, the efficiency of NK depletion was assessed by measuring the remaining lytic activity of spleen cells 3 days after a single injection of rabbit anti-Asialo GM1 antiserum. This was done using Yac-1 cells (American Type Culture Collection) as target cells in a conventional 51 Cr release assay (23). A single injection with 100 g of Ab was able to completely abrogate NK activity (not shown).…”

Section: In Vivo Depletion Experimentsmentioning

confidence: 99%

See 1 more Smart Citation

CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination

Casares

Arribillaga

Sarobe

et al. 2003

The Journal of Immunology

Self Cite

193

147

View full text Add to dashboard Cite

CD25+ regulatory T (T reg) cells suppress the activation/proliferation of other CD4+ or CD8+ T cells in vitro. Also, down-regulation of CD25+ T reg cells enhance antitumor immune responses. In this study, we show that depletion of CD25+ T reg cells allows the host to induce both CD4+ and CD8+ antitumoral responses following tumor challenge. Simultaneous depletion of CD25+ and CD8+ cells, as well as adoptive transfer experiments, revealed that tumor-specific CD4+ T cells, which emerged in the absence of CD25+ T reg cells, were able to reject CT26 colon cancer cells, a MHC class II-negative tumor. The antitumoral effect mediated by CD4+ T cells was dependent on IFN-γ production, which exerted a potent antiangiogenic activity. The capacity of the host to mount this antitumor response is lost once the number of CD25+ T reg cells is restored over time. However, CD25+ T reg cell depletion before immunization with AH1 (a cytotoxic T cell determinant from CT26 tumor cells) permits the induction of a long-lasting antitumoral immune response, not observed if immunization is conducted in the presence of regulatory cells. A study of the effect of different levels of depletion of CD25+ T reg cells before immunization with the peptide AH1 alone, or in combination with a Th determinant, unraveled that Th cells play an important role in overcoming the suppressive effect of CD25+ T reg on the induction of long-lasting cellular immune responses.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: In Vivo Depletion Experimentsmentioning

confidence: 99%

CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination

Casares

Arribillaga

Sarobe

et al. 2003

The Journal of Immunology

Self Cite

193

147

View full text Add to dashboard Cite

show abstract

“…To measure CTL activity, splenocytes (5 Â 10 6 cells/ml) from immunized mice were cultured in the presence of peptide E7(49-57) (10 lM) in culture medium. Five days later, lytic activity was measured by a conventional chromium release assay as described 22 using different numbers of effector cells and Na 2 51 CrO4-labeled EL-4 target cells incubated with or without peptide E7(49-57) (10 lM).…”

Section: Immunization Experiments and Measurement Of Immune Responsesmentioning

confidence: 99%

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin

Mansilla¹,

Berraondo²,

Durantez³

et al. 2011

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Cervical carcinoma is one of the most common cancers in women worldwide. It is well established that chronic infection of the genital tract by various mucosatropic human papillomavirus (HPV) types causes cervical cancer. Cellular immunity to E7 protein from HPV (HPVE7) has been associated with clinical and cytologic resolution of HPV-induced lesions. Thus, we decided to test if targeting of HPVE7 to dendritic cells using a fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for TLR4, and HPVE7 (EDA-HPVE7) might be an efficient vaccine for the treatment of cervical carcinoma. We found that EDA-HPVE7 fusion protein was efficiently captured by bone marrow derived dendritic cells in vitro and induced their maturation, with the upregulation of maturation markers and the production of IL-12. Immunization of mice with EDA-HPVE7 fusion protein induced antitumor CD8 1 T cell responses in the absence of additional adjuvants. Repeated intratumoral administration of EDA-HPVE7 in saline was able to cure established TC-1 tumors of 5-7 mm in diameter. More importantly, intravenous injection with EDA-HPVE7 in combination with the TLR ligand polyinosinic-polycytidylic acid (pIC), or with low doses of cyclophosphamide and the TLR9 ligand CpG-B complexed in cationic lipids, were able to eradicate large established TC-1 tumors (1.2 cm in diameter). Thus, therapeutic vaccination with EDA-HPVE7 fusion protein may be effective in the treatment of human cervical carcinoma.There is consistent evidence that chronic infection of the genital tract by various mucosatropic human papillomavirus (HPV) types cause cervical cancer. 1 In contrast to the prophylactic HPV vaccines that exhibit great promise in reducing the burden of cervical cancer, there is limited progress towards the development of immune therapeutic strategies for those women already infected with HPV who do not benefit from the current vaccines. The efficacy of these HPV vaccines correlates with the presence of serum neutralizing antibodies which may prevent virus infection (reviewed in ref. 2). However, it is believed that T cell immune responses, in particular against E7 protein, may play an important role in viral clearance and resolution of HPV-induced lesions. 3 Thus, a vaccination strategy able to activate a strong T cell immune response with the capacity to recognize and kill cancer cells expressing HPV proteins might be considered as therapeutic alternative for cervical carcinoma.Dendritic cells (DCs) are considered to be at the centre of acquired T cell responses due to their outstanding ability to capture antigens (Ag) and process them for their presentation as short peptides in the context of MHC molecules to naïve T cells. The unique capacity of DC to elicit immune responses has prompted many laboratories to use DC in clinical trials. However, ex vivo manipulation of DC for the production of DC-based vaccines is expensive, time consuming and difficult to standardize. Indeed, several variables, such as DC lineage, antigen loading to...

show abstract

“…Twelve to 15 days after immunization, spleens were removed, homogenized and 8 × 10 5 cells cultured in 96-well plates in RPMI-1640 medium supplemented with 10% fetal calf serum, antibiotics and 5 × 10 −5 M of 2-mercaptoethanol, in the presence or absence of peptide p1215 (10 g/ml). Five days later, cytotoxic activity was measured as previously described [44] using a conventional cytotoxicity assay using radio-labeled P815 cells pulsed with p1215 as target cells.…”

Section: Measurement Of Cytotoxic T Cell Activity After Immunization mentioning

confidence: 99%

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

Arribillaga

Sarobe

Arina

et al. 2005

Vaccine

Self Cite

View full text Add to dashboard Cite

The induction of protective or therapeutic cellular immunity against hepatitis C virus (HCV) is a difficult goal. In a previous work we showed that immunization with a recombinant adenovirus encoding HCV-NS3 (RAdNS3) could partially protect mice from challenge with a vaccinia virus encoding HCV antigens. We sought to investigate whether systemic administration of an immunostimulatory monoclonal antibody directed against the lymphocyte surface molecule CD137 could enhance the immunity elicited by RAdNS3. It was found that treatment with anti-CD137 mAb after the administration of a suboptimal dose of RAdNS3 enhanced cytotoxic and T helper cell responses against HCV NS3. Importantly, the ability of RAdNS3 to induce protective immunity against challenge with a recombinant vaccinia virus expressing HCV proteins was markedly augmented. Thus, combination of immunostimulatory anti-CD137 mAb with recombinant adenoviruses expressing HCV proteins might be useful in strategies of immunization against HCV.

show abstract

Induction of cytotoxic T lymphocytes in mice against the principal neutralizing domain of HIV-1 by immunization with an engineered T-cytotoxic-T-helper synthetic peptide construct

Cited by 40 publications

References 23 publications

CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination

CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

Contact Info

Product

Resources

About