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- Jeddi-Tehrani, Mahmood, et al.
(författare)
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Construction and characterization of a new chimeric antibody against HER2
- 2013
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Ingår i: Immunotherapy. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1750-743X .- 1750-7448.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Immunotherapy with anti-HER2 antibodies has shown promising results in patients with HER2-positive breast cancer. We have recently reported characterization of a mouse monoclonal antibody (mAb) against HER2, which binds to an epitope different from that recognized by trastuzumab and specifically inhibits proliferation of tumor cells overexpressing HER2. In the present study we report chimerization of this antibody. Materials & methods: The immunoglobulin variable region heavy and light chain genes of 1T0 hybridoma cells were amplified and ligated to human -1 and constant region genes using splice overlap extension PCR. The chimeric antibody was subsequently expressed and characterized by ELISA, western blot and flow cytometry. Results: The purified chimeric antibody specifically binds to recombinant HER2 and HER2-overexpressing tumor cells and inhibits proliferation of these cells. The binding affinity of the chimeric mAb was comparable with the parental mouse mAb. Conclusion: This chimeric anti-HER2 mAb is a potentially valuable tool for targeted immunotherapy.
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- Ahmadi, M, et al.
(författare)
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Immunization with HER2 extracellular subdomain proteins induces cellular response and tumor growth inhibition in mice
- 2018
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 10:6, s. 511-524
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We investigated cellular and protective immune responses in mice vaccinated with recombinant HER2 extracellular subdomains. Materials & methods: Balb/C mice were immunized with recombinant full HER2 extracellular domain and subdomain proteins. Humoral and cellular immune response and antitumor effect was evaluated using a syngeneic mice tumor model. Results: All recombinant proteins induced secretion of IL-4 and particularly IFN-γ and IL-17 cytokines. Challenging of immunized mice with stable 4T1-HER2 transfected cells resulted in partial but significant tumor growth inhibition in all groups of mice particularly those immunized with fHER2-ECD together with CPG. Conclusion: Our results suggest that the recombinant HER2-ECD subdomains induce mainly Th1 and Th17 responses, which seem to contribute to tumor growth inhibition in syngeneic mice.
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5. |
- Barkholt, L, et al.
(författare)
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Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study
- 2009
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 1:5, s. 753-764
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Tidskriftsartikel (refereegranskat)abstract
- The chimeric state after allogeneic hematopoietic stem cell transplantation provides a platform for adoptive immunotherapy using donor-derived immune cells. The major risk with donor lymphocyte infusions (DLIs) is the development of graft-versus-host disease (GvHD). Development of new DLI products with antitumor reactivity and reduced GvHD risk represents a challenging task in cancer immunotherapy. Although natural killer (NK) and NK-like T cells are promising owing to their antitumor activity, their low concentrations in peripheral blood mononuclear cells reduces their utility in DLIs. We have recently developed a system that allows expansion of clinical-grade NK and NK-like T cells in large numbers. In this study, the safety of donor-derived long-term ex vivo-expanded human NK and NK-like T cells given as DLIs was investigated as immunotherapy for cancer in five patients following allogeneic stem cell infusion. Infusion of the cells was safe whether administered alone or with IL-2 subcutaneously. No signs of acute GvHD were observed. One patient with hepatocellular carcinoma showed markedly decreased serum α-fetoprotein levels following cell infusions. These findings suggest that the use of ex vivo-expanded NK and NK-like T cells is safe and appears an attractive approach for further clinical evaluation in cancer patients.
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6. |
- Brodszki, Nicholas
(författare)
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Add-on or alone? Inhaled nebulized immunoglobulin reduces upper airway infections : 24 months of real-life experience
- 2020
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-743X .- 1750-7448. ; 12:6, s. 389-394
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with antibody deficiencies might suffer from acute/chronic upper respiratory tract infections (URTI), despite apparently adequate levels of replacement IgG. This pilot study aimed to ascertain whether inhaled nebulized immunoglobulin (INHIG) could reduce the number of URTI episodes. Methods: Three young, male sibling patients with antibody deficiency who, despite ongoing treatment, were suffering from frequent URTI and recurrent otitis media. INHIG consisted of 4 ml intravenous immunoglobulin (IVIG; 5%) nebulized with the eFLOW® nebulizer, twice daily. Data from meticulous infection symptoms diaries were used for analysis. Results: The patients tolerated the INHIG well; no adverse events were registered. The number of URTI was significantly decreased. Conclusion: In antibody deficient patients with URTI, INHIG reduces the incidence of URTI and may serve as a valuable physiological prophylaxis in the prevention of infections.
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7. |
- Dalianis, T
(författare)
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Immunotherapy for polyomaviruses: opportunities and challenges
- 2012
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 4:6, s. 617-628
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Tidskriftsartikel (refereegranskat)abstract
- Polyomaviruses are small DNA viruses present in mammals and birds, and in 1953 the first one to be described was murine polyomavirus. It was not until 1971 that the first two human polyomaviruses (HPyVs), BK virus and JC virus, were discovered and found to be common in humans, but only associated with disease in severely immunosuppressed patients. Since 2007, seven new HPyVs have been identified: KI polyomavirus, WU polyomavirus, Merkel cell polyomavirus, HPyV6, HPyV7, trichodyplasia spinulosa polyomavirus and HPyV9. Notably, Merkel cell polyomavirus was detected in Merkel cell cancer, a tumor mainly found in elderly and immunocompromised individuals, while trichodyplasia spinulosa polyomavirus was found in trichodyplasia spinulosa, a skin disorder observed only in immunosuppressed individuals. Consequently, many polyomaviruses cause problems in immunosuppressed individuals. This review deals with these issues, and the potential of the capsid protein VP1 to form virus-like particles for use as vaccines against polyomavirus infections.
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- Gardulf, A
(författare)
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Clinical experiences in primary and secondary immunodeficiencies and immune-mediated conditions using Gammanorm(®)
- 2016
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 8:5, s. 633-647
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Tidskriftsartikel (refereegranskat)abstract
- Treatment for primary and secondary immunodeficiency disorders focuses on prevention and management of infections, using immunoglobulin G (IgG) replacement therapy with regular intravenous or subcutaneous IgG (SCIG) infusions. SCIG therapy has many advantages including improved efficacy and tolerability, enhanced patient satisfaction and lower costs. A number of SCIG preparations are available, including Gammanorm®(Octapharma AG), a ready-to-use 16.5% liquid preparation of IgG, with low viscosity, well suited to self-administration and a long history of use. Clinical experience with Gammanorm has shown that it is effective and well tolerated in children and adults, including pregnant women, for primary and secondary immunodeficiency disorders. Recent data also suggest SCIG may have a role in the treatment of certain immune-mediated conditions.
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- Georgoudaki, AM, et al.
(författare)
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Suicide gene therapy for graft-versus-host disease
- 2010
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 2:4, s. 521-537
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Tidskriftsartikel (refereegranskat)abstract
- In allogeneic hematopoietic stem cell transplantation, donor-derived T cells are key players for early immune reconstitution and efficient engraftment, as well as the graft-versus-leukemia and graft-versus-infection effects. However, a severe and quite common life-threatening complication is the development of graft-versus-host disease, during which the alloreactive donor T cells attack the host. Controlling graft-versus-host disease while preserving the benefits of graft-versus-leukemia still constitutes a challenge. A promising approach for the control of graft-versus-host disease is suicide gene therapy, which involves the ex vivo genetic modification of donor T cells with a suicide gene that allows for the selective elimination of the cells in vivo if graft-versus-host disease occurs. This article presents an overview of such approaches with special reference to lessons learned from previous clinical experiences, as well as a discussion of critical factors in suicide gene therapy.
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10. |
- Jin, Chuan, et al.
(författare)
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Prospects to improve chimeric antigen receptor T-cell therapy for solid tumors
- 2016
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-743X .- 1750-7448. ; 8:12, s. 1355-1361
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Tidskriftsartikel (refereegranskat)abstract
- Adoptive transfer of patient-derived T-cells engineered with a chimeric antigen receptor (CAR) targeting the pan-B-cell marker CD19 has led to complete remission in patients with B-cell leukemias while response rates are more modest for B-cell lymphomas. This can be attributed to the fact that the semi-solid structure of lymphomas impedes T-cell infiltration and that the immune suppressive microenvironment within these tumors dampens the effect of CAR T-cells. These obstacles are even more pronounced for solid tumors where dense and often highly immunosuppressive structures are found. This article focuses on different aspects of how to improve CAR T-cells for solid tumors, primarily by decreasing their sensitivity to the harsh tumor microenvironment, by altering the immunosuppressive microenvironment inside tumors and by inducing bystander immunity.
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