Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine

Cobb, Amanda; Roberts, Lee K.; Palucka, A. Karolina; Mead, Holly; Ranganathan, Rajaram; Burkeholder, Susan; Finholt, Jennifer P; Blankenship, Derek; King, Bryan; Sloan, Louis; Harrod, Carson; Lévy, Yves; Banchereau, Jacques

doi:10.1016/j.jim.2010.11.002

Cited by 41 publications

(36 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These six DC vaccine batches were assessed for their ability to elicit HIV-antigen-specific autologous T-cell responses to the five peptide antigens present in the LIPO-5. Results demonstrate that CD4 + and CD8 + T-cells responses of IFN-ɣ-producing T-cells to the different HIV-antigens in the DC vaccines could be elicited by all of the HIV antigen lipopeptides, given that each patient had their unique and broad T-cell repertoires and HLA haplotypes [9]. Similar results were observed when the responding T cells were analyzed by measuring IL-13 production.…”

supporting

confidence: 63%

“…QC release of the DC vaccine for clinical use is based on the specified percentage of HLA-DR+CD11 + cells and CD80 + cells (Supporting Information Table 2). The characterization phenotype measures a large number of cell surface markers expressed by DC and associated with antigen-presenting activity.Functional characterization of vaccine DCs was reported in [9]. For this, DC vaccines were thawed and diluted tenfold with normal saline, washed by centrifugation and resuspended in complete RPMI media supplemented with 10% human serum type AB for coculture with autologous lymphocytes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

et al. 2014

Self Cite

View full text Add to dashboard Cite

Eur. J. Immunol. 2014Immunol. . 44: 2802Immunol. -2810 Clinical immunology 2803 IntroductionTo date, no effective therapeutic or prophylactic HIV vaccines are yet available. Recent encouraging results from the RV 144 trial showed a modest but statistically significant 31% reduction in the rate of HIV infection in vaccinated healthy volunteers receiving a prophylactic vaccine [1]. However, immune responses that would eradicate or control HIV are likely to be different from those needed to prevent primary infection. Indeed, eradication of HIV infection is likely to depend on the establishment of strong cytotoxic T lymphocytes, while prevention of infection will likely depend on the establishment of antibodies neutralizing the virus [2,3]. In both cases, CD4 + T helper cells are necessary for the establishment of robust and long-lasting immunity. Several candidate vaccines are under evaluation including peptides, inactivated virus, viral vectors, and ex vivo-generated DCs [4]. The latter represents an approach to optimize the induction of immune responses [5]. To date, only two studies, in which DCs have been loaded with chemically inactivated autologous virus, have reported a decrease in viral load [6,7]. Another approach using DCs transfected with RNA isolated from autologous virus yielded immune responses without control of viral replication [8]. However, these very promising data with inactivated autologous virus still need to be reproduced. For large scale use of DC vaccination, it would be advantageous to identify an antigenic cargo that could be used without having to isolate and expand the autologous virus which necessitates antiretroviral treatment interruption. We report here the safety and immunogenicity of a new DC platform loaded with five HIV-1-derived lipopeptides (LP) [9] in HIV-1-infected patients treated with highly active antiretroviral treatment (HAART). The study design included a 6-month analytical treatment interruption (ATI), a period which allowed us to evaluate the effects of vaccine-elicited immune responses on viral replication (Fig. 1). Results Patients and study outcomesTwenty patients were screened and 19 were enrolled within 17 months. Baseline characteristics of patients are reported in Table 1. All patients received the four vaccinations with no changes in vaccine dose. All patients but one completed the trial at 48 weeks.The vaccination was well tolerated. Two patients reached a safety endpoint (CD4 + T-cell counts below 500 cells/μL) during the vaccination phase while no safety endpoints were observed during the ATI phase. Systemic or local adverse events were mild or moderate (grade 1 or 2) and resolved in less than 2 days in the majority of cases. All patients stopped HAART at 24 weeks post inclusion except two of them who stopped at 25 and 26 weeks.Through 48 weeks, eight patients reached the immunology endpoint defining a failure of the strategy: at 28 (two patients), 32 (three patients), 36, 40, and 44 weeks. Three of these patients resumed HAART. No clinical events or pro...

show abstract

supporting

confidence: 63%

mentioning

confidence: 99%

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…The combination of GM-CSF and IFN-a was previously shown by other groups as recombinant cytokines (26,27) and also by us as transgenic cytokines (13) …”

Section: Discussionmentioning

confidence: 61%

Dendritic Cell–Mediated Immune Humanization of Mice: Implications for Allogeneic and Xenogeneic Stem Cell Transplantation

Salguero

Daenthanasanmak

Münz

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

De novo regeneration of immunity is a major problem after allogeneic hematopoietic stem cell transplantation (HCT). HCT modeling in severely compromised immune-deficient animals transplanted with human stem cells is currently limited because of incomplete maturation of lymphocytes and scarce adaptive responses. Dendritic cells (DC) are pivotal for the organization of lymph nodes and activation of naive T and B cells. Human DC function after HCT could be augmented with adoptively transferred donor-derived DC. In this study, we demonstrate that adoptive transfer of long-lived human DC coexpressing high levels of human IFN-α, human GM-CSF, and a clinically relevant Ag (CMV pp65 protein) promoted human lymphatic remodeling in immune-deficient NOD.Rag1−/−.IL-2rγ−/− mice transplanted with human CD34+ cells. After immunization, draining lymph nodes became replenished with terminally differentiated human follicular Th cells, plasma B cells, and memory helper and cytotoxic T cells. Human Igs against pp65 were detectable in plasma, demonstrating IgG class-switch recombination. Human T cells recovered from mice showed functional reactivity against pp65. Adoptive immunotherapy with engineered DC provides a novel strategy for de novo immune reconstitution after human HCT and a practical and effective tool for studying human lymphatic regeneration in vivo in immune deficient xenograft hosts.

show abstract

“…Наиболее часто ДК получают из моноцитов периферической крови человека [6,11]. Для получения моноцитов из периферической крови используют несколько подходов: выделение клеток крови, обладающих повышенной адгезией к поверхности культурального пластика [12], позитивную магнитную селекцию клеток, экспрессирующих рецептор CD14, с последующей негативной магнитной селекцией клеток, экспрессирующих рецепторы CD2 и CD19 [13], центрифугирование в градиенте плотности [12] и флотационные методы [14]. Количество и чистота моноцитов зависит от способа выделения.…”

Section: получение незрелых дендритных клеток из клеток предшественниковunclassified

Preparation of dendritic cells for cancer immunotherapy

Nazarkina

Laktionov

2015

BIOMED KHIM

View full text Add to dashboard Cite

Development of new effective method for cancer therapy is one of the most important trends in the modern medicine. Along with surgery, chemotherapy and radiotherapy, induction of an immune response against the tumor cells is a promising approach for therapy of cancer, particularly metastatic, slowly dividing tumors and cancer stem cells. Induction of the antitumor T-cell immune response involves activation of antigen-presenting cells, which can efficiently present the cancer antigens and activate T-lymphocytes. The immune response may be activated by dendritic cells (DC) loaded with tumor antigens, such as tumor-specific proteins, tumor cell lysates, apoptotic or necrotic tumor cells, as well as nucleic acids encoding tumor antigens. Regardless of the selected source of the tumor antigen, preparation of mature DC is a principal step in the development of anticancer vaccines aimed at the induction of the cytotoxic T-cell immune response. Recently, various research groups have proposed several strategies for producing mature DC, differed by the set of agents used. It has been shown that the maturation strategy influences both their phenotype and the ability to induce the immune response. In this review we have analyzed the results of studies on the various strategies of preparation of mature DCs.

show abstract

Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine

Cited by 41 publications

References 37 publications

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

Dendritic Cell–Mediated Immune Humanization of Mice: Implications for Allogeneic and Xenogeneic Stem Cell Transplantation

Preparation of dendritic cells for cancer immunotherapy

Contact Info

Product

Resources

About