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| 2. |
- Azharuddin, Mohammad, et al.
(författare)
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Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-imensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.
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| 3. |
- Azharuddin, Mohammad, 1986-, et al.
(författare)
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Nano toolbox in immune modulation and nanovaccines
- 2022
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Ingår i: Trends in Biotechnology. - Oxford, United Kingdom : Elsevier. - 0167-7799 .- 1879-3096. ; 40:10, s. 1195-1212
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Forskningsöversikt (refereegranskat)abstract
- Despite the great success of vaccines over two centuries, the conventional strategy is based on attenuated/altered microorganisms. However, this is not effective for all microbes and often fails to elicit a protective immune response, and sometimes poses unexpected safety risks. The expanding nano toolbox may overcome some of the roadblocks in vaccine development given the plethora of unique nanoparticle (NP)-based platforms that can successfully induce specific immune responses leading to exciting and novel solutions. Nanovaccines necessitate a thorough understanding of the immunostimulatory effect of these nanotools. We present a comprehensive description of strategies in which nanotools have been used to elicit an immune response and provide a perspective on how nanotechnology can lead to future personalized nanovaccines.
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| 4. |
- Boberg, Andreas, et al.
(författare)
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Immunization with HIV protease peptides linked to syngeneic erythrocytes
- 2007
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Ingår i: Infectious Agents and Cancer. - : Springer Science and Business Media LLC. - 1750-9378. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- New potent vaccine adjuvants are desirable for increasing the efficacy of novel vaccine modalities such as DNA and peptides. We therefore tested if syngeneic erythrocytes could serve as delivery vectors for selected HIV peptides and compared the potency of these constructs to immunization with peptides in phosphate buffered saline or in incomplete Freunds adjuvant Immunization of mice with peptides in a low dose (5 ng) coupled to erythrocytes induced a weak immune response in mice. These peptides alone (5 μg) gave no immune responses, while formulating the peptides (50 μg) in IFA induced strong homologous immunity as well as prominent cross reactivity to a related mutant epitope. Thus, vaccine delivery using syngeneic erythrocytes, although attractive for clinical use, might be of limited value due to the low amount of antigen that can be loaded per erythrocyte.
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| 5. |
- Boberg, Andreas, et al.
(författare)
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Murine models for HIV vaccination and challenge
- 2008
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Ingår i: Expert Review of Vaccines. - : Informa UK Limited. - 1476-0584 .- 1744-8395. ; 7:1, s. 117-130
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 only infects humans and chimpanzees. SIV or SHIV are, therefore, used as models for HIV in rhesus, cynomologus and pigtail macaques. Since conducting experiments in primate models does not fully mimic infection or vaccination against HIV-1 and is expensive, there is a great need for small-animal models in which it is possible to study HIV-1 infection, immunity and vaccine efficacy. This review summarizes the available murine models for studying HIV-1 infection with an emphasis on our experience of the HIV-1-infected-cell challenge as a model for evaluating candidate HIV-1 vaccines. In the cell-based challenge model, several important factors that, hopefully, can be related to vaccine efficacy in humans were discovered: the efficiency of combining plasmid DNA representing several of the viral genes originating from multiple clades of HIV-1, the importance of adjuvants activating innate and induced immunity and the enhanced HIV eradication by drug-conjugated antibody. © 2008 Future Drugs Ltd.
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| 6. |
- Boberg, Andreas, et al.
(författare)
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Receptor binding by cholera toxin B-subunit and amino acid modification improves minimal peptide immunogenecity
- 2012
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Ingår i: ISRN Molecular Biology. - : Hindawi Publishing Corporation. - 2090-7907. ; 2012
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Tidskriftsartikel (refereegranskat)abstract
- We increase our understanding of augmenting a cellular immune response, by using an HIV-1 protease-derived epitope (PR75−84), and variants thereof, coupled to the C-terminal, of the B subunit of cholera toxin (CTB). Fusion proteins were used for immunizations of HLA-A0201 transgenic C57BL/6 mice. We observed different capacities to elicit a cellular immune response by peptides with additions of five to ten amino acids to the PR epitope. There was a positive correlation between the magnitude of the elicited cellular immune response and the capacity of the fusion protein to bind GM-1. This binding capacity is affected by its ability to form natural pentamers of CTB. Our results suggest that functional CTB pentamers containing a foreign amino acid-modified epitope is a novel way to overcome the limited cellular immunogenicity of minimal peptide antigens. This way of using a functional assay as readout for improved cellular immunogenicity might become highly valuable for difficult immunogens such as short peptides (epitopes).
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| 7. |
- Brave, Andreas, et al.
(författare)
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Induction of HIV-1-specific cellular and humoral immune responses following immunization with HIV-DNA adjuvanted with activated apoptotic lymphocytes
- 2010
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Ingår i: VACCINE. - : Elsevier Science B.V.. - 0264-410X .- 1873-2518. ; 28:9, s. 2080-2087
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Tidskriftsartikel (refereegranskat)abstract
- Delivery of DNA encoding foreign antigens into mammalian cells can induce adaptive immune responses. There are currently many DNA-based vaccines in clinical trials against infectious diseases and cancer but there is a lack of adjuvants for improvement of responses to DNA-based vaccines. Here, we show augmented systemic and mucosa-associated B cell responses after immunization with a cocktail of seven different plasmids (3 env, 2 gag, 1 rev, 1 RT) combined with mitogen activated apoptotic syngeneic lymphocytes in mice. In addition we show that apoptotic cells can function as adjuvant for induction of cellular immune responses in a magnitude comparable to the cytokine adjuvant GM-CSF in mice. These data suggest that activated apoptotic lymphocytes can act independent as adjuvants to improve antigen-specific DNA vaccines.
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| 8. |
- Bråve, Andreas, et al.
(författare)
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Intranasal immunization of young mice with a multigene HIV-1 vaccine in combination with the N3 adjuvant induces mucosal and systemic immune responses
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:40, s. 5075-5078
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Tidskriftsartikel (refereegranskat)abstract
- One of the major challenges for the development of an HIV vaccine is to induce potent virus-specific immune responses at the mucosal surfaces where transmission of virus occurs. Intranasal delivery of classical vaccines has been shown to induce good mucosal antibody responses, but so far for genetic vaccines the success has been limited. This study shows that young individuals are sensitive to nasal immunization with a genetic vaccine delivered in a formulation of a lipid adjuvant, the Eurocine N3. Intranasal delivery of a multiclade/multigene HIV-1 genetic vaccine gave rise to vaginal and rectal IgA responses as well as systemic humoral and cellular responses. As electroporation might become the preferred means of delivering genetic vaccines for systemic HIV immunity, nasal delivery by droplet formulation in a lipid adjuvant might become a means of priming or boosting the mucosal immunity. © 2008 Elsevier Ltd. All rights reserved.
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| 9. |
- Bråve, Andreas, et al.
(författare)
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Maternal immune status influences HIV-specific immune responses in pups after DNA prime protein boost using mucosal adjuvant
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:47, s. 5957-5966
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to determine the impact of maternal HIV-1 specific immunity on HIV-DNA immunization of 2 weeks old pups during the breast-feeding period. Adult female mice received intranasal or intradermal HIV DNA (gp160Env, p37Gag, Nef, Tat and Rev) prime and recombinant protein booster immunizations that induced mucosal and systemic HIV-1 specific B and T cell responses. Intranasal administration of the immunogens induced higher serum IgG titers to HIV antigens than the intradermal immunization. Furthermore, predominantly higher HIV-1 specific fecal IgA titers were obtained in nasally immunized mice. The capacity to respond to one single prime with DNA and one boost with recombinant protein was then compared in pups born to mothers displaying HIV-1-specific immune responses and in pups born to non-vaccinated mothers. Immune responses to the greatest number of antigens were detected in pups born to mothers having the highest HIV-1 specific immune responses. These data suggest that HIV-1 DNA-plasmid immunization during breast-feeding and recombinant protein boosting shortly thereafter enhances the breadth of the humoral HIV-1 specific immune responses.
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| 10. |
- Buonaguro, L, et al.
(författare)
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DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity
- 2007
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 25:32, s. 5968-5977
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Tidskriftsartikel (refereegranskat)abstract
- The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the heterologous prime-boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3. © 2007 Elsevier Ltd. All rights reserved.
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