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  1. AU="Anne Fåne"
  2. AU=Liang John W
  3. AU="Segura-Martínez, Patricia"
  4. AU="Cao, Xi-Ming"
  5. AU="Labaronne, Emmanuel"
  6. AU="Shimpukade, Bharat"
  7. AU="Claude, Pierre-Abel"
  8. AU="Rocha Vogel, Angus"
  9. AU="Larkin, J"
  10. AU="Gilbert, A."
  11. AU="Jérémie Bruno"
  12. AU="Barg, Alexej"
  13. AU="Niranjan, M"
  14. AU="Solomon, Hilla"
  15. AU="de Aguiar Junior, Francisco Carlos Amanajás"
  16. AU=Carley David W
  17. AU="Solvig Ekblad"
  18. AU=Gibertoni Dino
  19. AU="Sein, Maung Kyaw"
  20. AU="Yun-Fei Xia"

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  1. Artikel ; Online: A TCR-based Chimeric Antigen Receptor

    Even Walseng / Hakan Köksal / Ibrahim M. Sektioglu / Anne Fåne / Gjertrud Skorstad / Gunnar Kvalheim / Gustav Gaudernack / Else Marit Inderberg / Sébastien Wälchli

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Band 10

    Abstract: Abstract Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, ...

    Abstract Abstract Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells. Hence, an introduced therapeutic TCR will compete with the endogenous TCR for the signalling proteins and carries the potential risk of mixed dimer formation giving rise to a new TCR with unpredictable specificity. We have fused a soluble TCR construct to a CAR-signalling tail and named the final product TCR-CAR. We here show that, if expressed, the TCR-CAR conserved the specificity and the functionality of the original TCR. In addition, we demonstrate that TCR-CAR redirection was not restricted to T cells. Indeed, after transduction, the NK cell line NK-92 became TCR positive and reacted against pMHC target. This opens therapeutic avenues combing the killing efficiency of NK cells with the diversified target recognition of TCRs.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2017-09-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma

    Nadia Mensali / Hakan Köksal / Sandy Joaquina / Patrik Wernhoff / Nicholas P. Casey / Paola Romecin / Carla Panisello / René Rodriguez / Lene Vimeux / Asta Juzeniene / Marit R. Myhre / Anne Fåne / Carolina Castilla Ramírez / Solrun Melkorka Maggadottir / Adil Doganay Duru / Anna-Maria Georgoudaki / Iwona Grad / Andrés Daniel Maturana / Gustav Gaudernack /
    Gunnar Kvalheim / Angel M. Carcaboso / Enrique de Alava / Emmanuel Donnadieu / Øyvind S. Bruland / Pablo Menendez / Else Marit Inderberg / Sébastien Wälchli

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Band 15

    Abstract: Abstract Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and ... ...

    Abstract Abstract Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform of alkaline phosphatase, ALPL-1, which is highly and specifically expressed in primary and metastatic OS. The target recognition element of the second-generation CAR construct is based on two antibodies, previously shown to react against OS. T cells transduced with these CAR constructs mediate efficient and effective cytotoxicity against ALPL-positive cells in in vitro settings and in state-of-the-art in vivo orthotopic models of primary and metastatic OS, without unexpected toxicities against hematopoietic stem cells or healthy tissues. In summary, CAR-T cells targeting ALPL-1 show efficiency and specificity in treating OS in preclinical models, paving the path for clinical translation.
    Schlagwörter Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2023-06-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: NK cells specifically TCR-dressed to kill cancer cellsResearch in context

    Nadia Mensali / Pierre Dillard / Michael Hebeisen / Susanne Lorenz / Theodossis Theodossiou / Marit Renée Myhre / Anne Fåne / Gustav Gaudernack / Gunnar Kvalheim / June Helen Myklebust / Else Marit Inderberg / Sébastien Wälchli

    EBioMedicine, Vol 40, Iss , Pp 106-

    2019  Band 117

    Abstract: Background: Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and ...

    Abstract Background: Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and expensive process which could be resolved by the use of universal cells. Currently, only the Natural Killer (NK) cell line NK-92 is FDA approved for universal use. In order to expand their recognition ability, they were equipped with Chimeric Antigen Receptors (CARs). However, unlike CARs, T-cell receptors (TCRs) can recognize all cellular proteins, which expand NK-92 recognition to the whole proteome. Methods: We herein genetically engineered NK-92 to express the CD3 signaling complex, and showed that it rendered them able to express a functional TCR. Functional assays and in vivo efficacy were used to validate these cells. Findings: This is the first demonstration that a non-T cell can exploit TCRs. This TCR-redirected cell line, termed TCR-NK-92, mimicked primary T cells phenotypically, metabolically and functionally, but retained its NK cell effector functions. Our results demonstrate a unique manner to indefinitely produce TCR-redirected lymphocytes at lower cost and with similar therapeutic efficacy as redirected T cells. Interpretation: These results suggest that an NK cell line could be the basis for an off-the-shelf TCR-based cancer immunotherapy solution. Fund: This work was supported by the Research Council of Norway (#254817), South-Eastern Norway Regional Health Authority (#14/00500-79), by OUS-Radiumhospitalet (Gene Therapy program) and the department of Oncology at the University of Lausanne. Keywords: Immunotherapy, TCR, T cell, Natural killer
    Schlagwörter Medicine ; R ; Medicine (General) ; R5-920
    Thema/Rubrik (Code) 570 ; 610
    Sprache Englisch
    Erscheinungsdatum 2019-02-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Neurotropic Threat Characterization of Burkholderia pseudomallei Strains

    Jodie L. Morris / Anne Fane / Catherine M. Rush / Brenda L. Govan / Mark Mayo / Bart J. Currie / Natkunam Ketheesan

    Emerging Infectious Diseases, Vol 21, Iss 1, Pp 58-

    2015  Band 63

    Abstract: The death rate for neurologic melioidosis is high. Whether certain Burkholderia pseudomallei strains are more likely than other strains to cause central nervous system infection and whether route of infection influences the neurotropic threat remain ... ...

    Abstract The death rate for neurologic melioidosis is high. Whether certain Burkholderia pseudomallei strains are more likely than other strains to cause central nervous system infection and whether route of infection influences the neurotropic threat remain unclear. Therefore, we compared the virulence and dissemination of Australian clinical isolates collected during October 1989–October 2012 from patients with neurologic and nonneurologic melioidosis after intranasal and subcutaneous infection of mice in an experimental model. We did not observe neurotropism as a unique characteristic of isolates from patients with neurologic melioidosis. Rather, a distinct subset of B. pseudomallei strains appear to have heightened pathogenic potential for rapid dissemination to multiple tissues, including the central nervous system, irrespective of the infection route. This finding has valuable public health ramifications for initiating appropriate and timely therapy after exposure to systemically invasive B. pseudomallei strains. Increasing understanding of B. pseudomallei pathology and its influencing factors will further reduce illness and death from this disease.
    Schlagwörter neurologic ; melioidosis ; Burkholderia pseudomallei ; route of infection ; virulence ; neurotropism ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Centers for Disease Control and Prevention
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei–like Variation in the bimA Motility Gene, Australia

    Jodie L. Morris / Anne Fane / Derek Sarovich / Erin P. Price / Catherine M. Rush / Brenda L. Govan / Elizabeth Parker / Mark Mayo / Bart J. Currie / Natkunam Ketheesan

    Emerging Infectious Diseases, Vol 23, Iss 5, Pp 740-

    2017  Band 749

    Abstract: Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to ... ...

    Abstract Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system. In this study, we demonstrate that this subset has a B. mallei–like sequence variation of the actin-based motility gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles, isolates that contain the B. mallei–like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health.
    Schlagwörter melioidosis ; Burkholderia pseudomallei ; virulence ; neurologic ; neurotropism ; route of infection ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2017-05-01T00:00:00Z
    Verlag Centers for Disease Control and Prevention
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Predicted Coverage and Immuno-Safety of a Recombinant C-Repeat Region Based Streptococcus pyogenes Vaccine Candidate.

    Celia McNeilly / Samantha Cosh / Therese Vu / Jemma Nichols / Anna Henningham / Andreas Hofmann / Anne Fane / Pierre R Smeesters / Catherine M Rush / Louise M Hafner / Natkuman Ketheesan / Kadaba S Sriprakash / David J McMillan

    PLoS ONE, Vol 11, Iss 6, p e

    2016  Band 0156639

    Abstract: The C-terminal region of the M-protein of Streptococcus pyogenes is a major target for vaccine development. The major feature is the C-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. SV1 is a S. ... ...

    Abstract The C-terminal region of the M-protein of Streptococcus pyogenes is a major target for vaccine development. The major feature is the C-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. SV1 is a S. pyogenes vaccine candidate that incorporates five 14mer amino acid sequences (called J14i variants) from differing C-repeat units in a single recombinant construct. Here we show that the J14i variants chosen for inclusion in SV1 are the most common variants in a dataset of 176 unique M-proteins. Murine antibodies raised against SV1 were shown to bind to each of the J14i variants present in SV1, as well as variants not present in the vaccine. Antibodies raised to the individual J14i variants were also shown to bind to multiple but different combinations of J14i variants, supporting the underlying rationale for the design of SV1. A Lewis Rat Model of valvulitis was then used to assess the capacity of SV1 to induce deleterious immune response associated with rheumatic heart disease. In this model, both SV1 and the M5 positive control protein were immunogenic. Neither of these antibodies were cross-reactive with cardiac myosin or collagen. Splenic T cells from SV1/CFA and SV1/alum immunized rats did not proliferate in response to cardiac myosin or collagen. Subsequent histological examination of heart tissue showed that 4 of 5 mice from the M5/CFA group had valvulitis and inflammatory cell infiltration into valvular tissue, whereas mice immunised with SV1/CFA, SV1/alum showed no sign of valvulitis. These results suggest that SV1 is a safe vaccine candidate that will elicit antibodies that recognise the vast majority of circulating GAS M-types.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2016-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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