Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]

Apostolopoulos, Vasso; Pietersz, Geoffrey A.; Tsibanis, Anastasios; Tsikkinis, Annivas; Drakaki, Heleni; Loveland, Bruce E.; Piddlesden, Sara J.; Plebanski, Magdalena; Pouniotis, Dodie; Alexis, Μichael N.; McKenzie, Ian F. C.; Vassilaros, Stamatis

doi:10.1186/bcr1505

Cited by 154 publications

(90 citation statements)

References 38 publications

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“…In a randomized, double-blind study, patients with stage II breast cancer but no evidence of disease received injections with oxidized mannan-mucin 1 (MUC1) to immunize against MUC1 and to prevent cancer recurrence/metastases. 56 Immunized patients had no recurrences (0 of 16 patients) for >5 years after treatment, whereas the recurrence rate among patients who received placebo was 27% (4 of 15 patients). In the majority of vaccinated patients, both humoral and cellular immunity to MUC1 was evident.…”

Section: Immunogenic Her-2/neu Peptides and Ii-key/her-2/neu Hybrid Pmentioning

confidence: 94%

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

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The use of synthetic peptides as vaccines aimed at the induction of therapeutic CD8-positive T-cell responses against tumor cells initially experienced great enthusiasm, mostly because of advances in vaccine technology, including design, synthesis, and delivery. However, despite impressive results in animal models, the application of such vaccines in humans has met with only limited success. The therapeutic activity of vaccine-stimulated, tumor-specific, CD8-positive T cells can be hampered through the physical burden of the tumor, tolerance mechanisms, and local factors within the tumor microenvironment. Recently, accumulating evidence has suggested that combining a peptide-based therapeutic vaccination with conventional chemotherapy can uncover the full potential of the antitumor immune response, increasing the success of immunotherapy. In addition, therapeutic vaccination in the preventive setting has been extremely effective in eliciting antitumor responses in preclinical tumor models and has demonstrated good promise clinically in patients with minimal residual disease. The rationale behind preventive vaccination is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses. Finally, therapeutic CD8-positive T-cell peptide vaccines have been improved by coimmunization with T-helper epitopes expressed on long peptides.

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Section: Immunogenic Her-2/neu Peptides and Ii-key/her-2/neu Hybrid Pmentioning

confidence: 94%

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

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“…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

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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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“…Most previous studies have focused on the use of a synthetic peptide, either by itself or conjugated to a carrier protein (Chung et al 2003;Apostolopoulos et al 2006;Kohlgraf et al 2004;North and Butts 2005). However, peptide vaccines may possess certain disadvantages.…”

Section: Discussionmentioning

confidence: 97%