Up to 15-year Clinical Follow-Up of a Pilot Phase III Immunotherapy Study in Stage II Breast Cancer Patients Using Oxidized Mannan–MUC1

Vassilaros, Stamatis; Tsibanis, Anastasios; Tsikkinis, Annivas; Pietersz, Geoffrey A.; Apostolopoulos, Vasso

doi:10.2217/imt.13.126

Cited by 94 publications

(81 citation statements)

References 19 publications

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“…DC in particular are proficient in processing exogenous antigens for presentation by class I molecules via the cross-presentation pathway [58]. Most adjuvants have properties or are designed to access one or both of these pathways using a number of mechanisms such as the nature of the particulate (microparticles, VLP, ISCOM) [59][60][61][62], having membrane fuseogenic properties (liposomes, ISCOM) [63,64] or cell surface receptor binding (mannan or recombinant antibody) [3,4,6,8].…”

Section: Efficient Generation Of Cd8mentioning

confidence: 99%

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Vaccine delivery by penetratin: mechanism of antigen presentation by dendritic cells

et al. 2016

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Cell penetrating peptides (CPP) or membrane translocating peptides such as, penetratin from Antennapedia homeodomain or TAT from human immunodeficiency virus are useful vectors for the delivery of protein antigens or their cytotoxic (Tc) or helper (Th) T cell epitopes to antigen presenting cells. Mice immunized with CPP containing immunogens elicit antigen-specific Tc and/or Th responses and could be protected from tumor challenges. In the present paper, we investigate the mechanism of class I and class II antigen presentation of ovalbumin covalently linked to penetratin (AntpOVA) by bone marrow-derived dendritic cells (BMDC) with the use of biochemical inhibitors of various pathways of antigen processing and presentation. Results from our study suggested that uptake of AntpOVA is via a combination of energy independent (membrane fusion) and energy dependent pathways (endocytosis). Once internalized by either mechanism, multiple tap-dependent or independent antigen presentation pathways are accessed whilst not completely dependent on proteasomal processing but involving proteolytic trimming in the ER and Golgi compartments. Our study provides an understanding on the mechanism of antigen presentation mediated by CPP and leads to greater insights into future development of vaccine formulations.

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Section: Efficient Generation Of Cd8mentioning

confidence: 99%

“…Studies have identified receptors on various DC subtypes that are efficient in generating immune responses [3,4]. There are also multiple approaches reported for the targeted delivery of antigens to some of these receptors expressed on DC and few vaccines are currently in clinical trials [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Vaccine delivery by penetratin: mechanism of antigen presentation by dendritic cells

et al. 2016

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“…При окислительном связывании с рекомбинантным белковым антигеном и последующем интраназальном его введении маннан усиливал выработку антиген-специфических сывороточных и секреторных антител у мышей F1 и C57BL. В клиническом исследовании антигена MUC-1 (антиген, экс-прессируемый различными опухолями, в данном случае аде-нокарциномой), конъюгированного с окисленным маннаном, частота рецидивирования опухоли была более чем в четыре С. С. Курашова, Т. К. Дзагурова, А. А. Ишмухаметов, М. С. Егорова, М. В. Баловнева, С. Е. Соцкова, Е. А. Ткаченко S. S. Kurashova, Т. К. Dzagurova, А. А. Ishmukhametov, М. S. Egorova, М. V. Balovneva, S. E. Sotskova, Е. А. Tkachenko раза ниже [43]. При конъюгации основного миелинового белка (ОМБ) с восстановленным маннаном иммунный ответ против ОМБ реализовывался не Th1, а Th2, что предотвращало раз-витие экспериментального аллергического энцефаломиелита у мышей [44].…”

Section: маннановые адъювантыunclassified

Carbohydrate-Based Adjuvants for Vaccine Production

Курашова¹,

Dzagurova²,

Ishmukhametov³

et al. 2018

Biopreparaty. Profilaktika, diagnostika, lechenie

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“…The median survival times were 23.1 months and 22.3 months, respectively [Miles et al 2011]. An oxidized mannan-MUC1 vaccine showed, in the adjuvant setting, an encouraging reduction in recurrence rate (12.5% versus 60% in the placebo arm) after 15 years of follow up [Vassilaros et al 2013].…”

Section: Ctla-4mentioning

confidence: 99%

Strategies to modulate the immune system in breast cancer: checkpoint inhibitors and beyond

et al. 2016

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Is breast cancer (BC) immunogenic? Many data suggest that it is. Many observations demonstrated the prognostic role of tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2 (HER-2)-positive BC. TNBCs are poorly differentiated tumors with high genetic instability and very high heterogeneity. This heterogeneity enhances the ‘danger signals’ and select clone variants that could be more antigenic or, in other words, that could more strongly stimulate a host immune antitumor response. The response to chemotherapy is at least partly dependent on an immunological reaction against those tumor cells that are dying during the chemotherapy. One of the mechanisms whereby chemotherapy can stimulate the immune system to recognize and destroy malignant cells is commonly known as immunogenic cell death (ICD). ICD elicits an adaptive immune response. Which are the clinical implications of all ‘immunome’ data produced in the last years? First, validate prognostic or predictive role of TILs. Second, validate immune genomic signatures that may be predictive and prognostic in patients with TN disease. Third, incorporate an ‘immunoscore’ into traditional classification of BC, thus providing an essential prognostic and potentially predictive tool in the pathology report. Fourth, implement clinical trials for BC in the metastatic setting with drugs that target immune-cell–intrinsic checkpoints. Blockade of one of these checkpoints, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) or the programmed cell death 1 (PD-1) receptor may provide proof of concepts for the activity of an immune-modulation approach in the treatment of a BC.

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Up to 15-year Clinical Follow-Up of a Pilot Phase III Immunotherapy Study in Stage II Breast Cancer Patients Using Oxidized Mannan–MUC1

Cited by 94 publications

References 19 publications

Vaccine delivery by penetratin: mechanism of antigen presentation by dendritic cells

Vaccine delivery by penetratin: mechanism of antigen presentation by dendritic cells

Carbohydrate-Based Adjuvants for Vaccine Production

Strategies to modulate the immune system in breast cancer: checkpoint inhibitors and beyond

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