Ex vivo targeting of the macrophage mannose receptor generates anti-tumor CTL responses

Apostolopoulos, Vasso; Barnes, Nadine; Pietersz, Geoffrey A.; McKenzie, Ian F. C.

doi:10.1016/s0264-410x(00)00090-6

Cited by 117 publications

(109 citation statements)

References 33 publications

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“…Although the failure of the first anti-Aβ-immunotherapy clinical trial was disappointing, the follow-up studies indicate that Th2-prone immune response may be more beneficial and safer than a Th1 response. Mannan has previously been shown to be a potent molecular adjuvant enhancing both B-and T-cell immune responses, as well as antigen uptake and presentation (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,2000Engering et al, 1997aEngering et al, ,1997bKaranikas et al, 1997;Gröger et al, 2000;Linehan et al, 2000;Vaughan et al, 2000;Stambas et al, 2002aStambas et al, ,2002bStambas et al, ,2005. This molecular adjuvant not only enhanced antibody responses specific to appropriate peptide attached to it (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,2000, but under certain conditions also induced Th2-polarized immunity (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,1996Vaughan et al, 1999;Apostolopoulos and McKenzie, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Besides promoting phagocytosis and antigen presentation, antigens conjugated to mannan may also provide a stronger signal to antigen-specific B cells by simultaneous triggering of BCR and CD21 and/or BCR and CD35 C' receptors (Molina et al, 1996;Kozono et al, 1998). Enhancement of immune responses against several mannosylated antigens, including peptide antigens, has been demonstrated (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,2000. Under certain conditions, mannosylated antigens induced strong Th2 type anti-inflammatory responses with high levels of IgG1 antibodies, IL4 and IL10 production (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, ,1996Vaughan et al, 1999;Apostolopoulos and McKenzie, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Mannan has been investigated extensively as a molecular adjuvant due to its ability to enhance both B-and T-cell immune responses (Okawa et al, 1992;Apostolopoulos et al, 1995Apostolopoulos et al, , 2000Karanikas et al, 1997;Vaughan et al, 2000;Stambas et al, 2002aStambas et al, ,2002bStambas et al, ,2005. The adjuvant function is dependent on the ability to target the immunogen to antigen-presenting cells expressing receptors specific to mannosylated sugars.…”

Section: Introductionmentioning

confidence: 99%

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Aβ-Immunotherapy for Alzheimer's Disease Using Mannan–Amyloid-Beta Peptide Immunoconjugates

Ghochikyan

Petrushina

Lees³

et al. 2006

DNA and Cell Biology

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In Alzheimer's disease (AD) the accumulation of pathological forms of the beta-amyloid (Aβ) peptide are believed to be causal factors in the neurodegeneration that results in the loss of cognitive function in patients. Anti-Aβ antibodies have been shown to reduce Aβ levels in transgenic mouse models of AD and in AN-1792 clinical trial on AD patients; however, the clinical trial was halted when some patients developed meningoencephalitis. Theories on the cause of the adverse events include proinflammatory "primed patients," a Th1-inducing adjuvant, and Aβ autoreactive T cells. New immunotherapy approaches are being developed to eliminate these putative risk factors. Mannan, which is recognized by pattern recognition receptors of the innate immune system, can be utilized as a molecular adjuvant to promote a Th2-mediated immune response to conjugated B cell epitopes. The N-terminus of Aβ was conjugated to mannan, and used to immunize mice with low concentrations of immunoconjugate, without a conventional adjuvant. Mannan induced a significant and highly polarized toward Th2 phenotype anti-Aβ antibody response not only in BALB/c, but also in B6SJL F1 mice. New preclinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse immune response that occurred in the first clinical trial.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aβ-Immunotherapy for Alzheimer's Disease Using Mannan–Amyloid-Beta Peptide Immunoconjugates

Ghochikyan

Petrushina

Lees³

et al. 2006

DNA and Cell Biology

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“…Extensive O-mannosylation of proteins greatly enhanced antigen delivery, and deglycosylation profoundly inhibited T cell responses [7]. The role of mannose residues in antigen delivery was also shown by the mannose polymer, mannan, which enhanced antigen-specific Th1/CTL and Th2/antibody responses in oxidized and reduced forms, respectively [9][10][11][12][13][14][15]. Oxidized mannan conjugated to recombinant MUC1 fusion protein has been used in Phase II/III cancer clinical trials [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

et al. 2008

Self Cite

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Antigen mannosylation has been shown to be an effective approach to potentiate antigen immunogenicity, due to the enhanced antigen uptake and presentation by APC. To overcome disadvantages associated with conventional methods used to mannosylate antigens, we have developed a novel mannose-based antigen delivery system that utilizes a polyamidoamine (PAMAM) dendrimer. It is demonstrated that mannosylated dendrimer ovalbumin (MDO) is a potent immune inducer. With a strong binding avidity to DC, MDO potently induced OVA-specific T cell response in vitro. It was found that the immunogenicity of MDO was due not only to enhanced antigen presentation, but also to induction of DC maturation. Mice immunized with MDO generated strong OVA-specific CD4 + /CD8 + T cell and antibody responses. MDO also targeted lymph node DC to crosspresent OVA, leading to OTI CD8 + T cell proliferation. Moreover, upon challenge with B16-OVA tumor cells, tumors in mice pre-immunized with MDO either did not grow or displayed a much more delayed onset, and had slower kinetics of growth than those of OVA-immunized mice. This mannose-based antigen delivery system was applied here for the first time to the immunization study. With several advantages and exceptional adjuvanticity, we propose mannosylated dendrimer as a potential vaccine carrier.

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“…This is consistent with other reports stating that targeting to the mannose receptor can induce a strong immune response due to receptor-mediated endocytosis and hence better uptake Values are expressed as mean ± SD, n ¼ 3. (Apostolopoulos et al, 2000;Engering et al, 1997a,b). It is well-known fact that the mannose receptor functions as a potential antigen receptor in the dendritic cells.…”

Section: Acidic Degradation Protein Assaymentioning

confidence: 99%

Development and characterization of guar gum nanoparticles for oral immunization against tuberculosis

et al. 2014

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The main aim of this study was to develop an effective carrier system containing Ag85A-loaded guar gum nanoparticles for oral vaccination against tuberculosis. Nanoparticles were prepared by Nanoprecipitation method. The developed particles with mean diameter 895.5 ± 14.73 nm and high antigen entrapment seem to be optimum for oral vaccine delivery. The acid protection assay, Peyer's patch uptake study and in-vitro antigen study confirmed that the developed formulations can protect the antigen from harsh gastric environment and can safely deliver the antigen to the intestinal region. In vivo studies data indicated that the developed nanocarriers can induce a strong mucosal as well as systemic immune response. Therefore, the experimental evidence suggests that guar-gum nanoparticle findings indicated that the guar gum nanoparticles can be utilized for safe and effective vaccine delivery via oral route.

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Ex vivo targeting of the macrophage mannose receptor generates anti-tumor CTL responses

Cited by 117 publications

References 33 publications

Aβ-Immunotherapy for Alzheimer's Disease Using Mannan–Amyloid-Beta Peptide Immunoconjugates

Aβ-Immunotherapy for Alzheimer's Disease Using Mannan–Amyloid-Beta Peptide Immunoconjugates

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

Development and characterization of guar gum nanoparticles for oral immunization against tuberculosis

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