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Article ; Online: Chronic GVHD on the move.

Müller, Antonia M S

2022 Volume 140, Issue 25, Page(s) 2660–2661

MeSH term(s)	Humans ; Hematopoietic Stem Cell Transplantation/adverse effects ; Graft vs Host Disease/etiology ; Bronchiolitis Obliterans Syndrome ; T-Lymphocytes, Helper-Inducer
Language	English
Publishing date	2022-12-22
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022018321
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Article: Chemotherapie-freie Behandlung von hämatologischen Neoplasien: Zukunftstraum oder beginnende Realität?

Ring, Alexander / Müller, Antonia M S

Praxis

2019 Volume 108, Issue 6, Page(s) 411–418

Abstract: Chemotherapy-Free Treatment of Hematological Neoplasias: Dream or Reality? ...

Title translation	Chemotherapy-Free Treatment of Hematological Neoplasias: Dream or Reality?
Abstract	Chemotherapy-Free Treatment of Hematological Neoplasias: Dream or Reality?
MeSH term(s)	Hematologic Neoplasms/therapy ; Humans ; Immunotherapy
Language	German
Publishing date	2019-04-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	209026-0
ISSN	1661-8165 ; 1661-8157 ; 0369-8394
ISSN (online)	1661-8165
ISSN	1661-8157 ; 0369-8394
DOI	10.1024/1661-8157/a003230
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Article: Better by design: What to expect from novel CAR-engineered cell therapies?

Luginbuehl, Vera / Abraham, Eytan / Kovar, Karin / Flaaten, Richard / Müller, Antonia M S

Biotechnology advances. 2022 Sept., v. 58

2022

Abstract: Chimeric antigen receptor (CAR) technology, and CAR-T cells in particular, have emerged as a new and powerful tool in cancer immunotherapy since demonstrating efficacy against several hematological malignancies. However, despite encouraging clinical ... ...

Abstract	Chimeric antigen receptor (CAR) technology, and CAR-T cells in particular, have emerged as a new and powerful tool in cancer immunotherapy since demonstrating efficacy against several hematological malignancies. However, despite encouraging clinical results of CAR-T cell therapy products, a significant proportion of patients do not achieve satisfactory responses, or relapse. In addition, CAR-T cell applications to solid tumors is still limited due to the tumor microenvironment and lack of specifically targetable tumor antigens. All current products on the market, as well as most investigational CAR-T cell therapies, are autologous, using the patient's own peripheral blood mononuclear cells as starting material to manufacture a patient-specific batch. Alternative cell sources are, therefore, under investigation (e.g. allogeneic cells from an at least partially human leukocyte antigen (HLA)-matched healthy donor, universal “third-party” cells from a non-HLA-matched donor, cord blood-derived cells, immortalized cell lines or cells differentiated from induced pluripotent stem cells). However, genetic modifications of CAR-engineered cells, bioprocesses used to expand cells, and improved supply chains are still complex and costly. To overcome drawbacks associated with CAR-T technologies, novel CAR designs have been used to genetically engineer cells derived from alpha beta (αβ) T cells, other immune cells such as natural killer (NK) cells, gamma delta (γδ) T cells, macrophages or dendritic cells. This review endeavours to trigger ideas on the next generation of CAR-engineered cell therapies beyond CAR-T cells and, thus, will enable effective, safe and affordable therapies for clinical management of cancer. To achieve this, we present a multidisciplinary overview, addressing a wide range of critical aspects: CAR design, development and manufacturing technologies, pharmacological concepts and clinical applications of CAR-engineered cell therapies. Each of these fields employs a large number of ground-breaking scientific advances, where coordinated and complex process and product development occur at their interfaces.
Keywords	HLA antigens ; biotechnology ; immunotherapy ; macrophages ; markets ; neoplasms ; patients ; product development ; relapse
Language	English
Dates of publication	2022-09
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	47165-3
ISSN	0734-9750
ISSN	0734-9750
DOI	10.1016/j.biotechadv.2022.107917
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Complement inhibition for the treatment of COVID-19 triggered thrombotic microangiopathy with cardiac failure: a case report.

Utebay, Didar / Seeger, Harald / Müller, Antonia M S / David, Sascha

European heart journal. Case reports

2021 Volume 5, Issue 10, Page(s) ytab386

Abstract: Background: Severe coronavirus disease 2019 (COVID-19) has been increasingly recognized as a multisystem disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect literally any cell type that expresses its target receptor ... ...

Abstract	Background: Severe coronavirus disease 2019 (COVID-19) has been increasingly recognized as a multisystem disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect literally any cell type that expresses its target receptor angiotensin-converting enzyme 2. However, COVID-19-associated organ dysfunction is not only mediated by direct viral effects but also by the interaction between the host's immune response, endotheliopathy, and microvascular coagulopathy. It has been proposed that the activation of the complement system plays a central role in the pathophysiology of severe COVID-19 and the associated endotheliopathy. Case summary: A 76-year-old male patient with indeterminate cardiogenic shock in the setting of confirmed SARS-CoV-2 infection was admitted to our intensive care unit. Coronary angiography did not reveal a plausible explanation for his symptoms. The patient developed renal failure, neurological symptoms, severe thrombocytopenia, and a Coombs-negative haemolytic anaemia with schistocytes. All together the clinical picture was highly suggestive of a thrombotic microangiopathy (TMA) with microvascular cardiac involvement. Conventional therapeutic strategies including high-dose steroids and seven sessions of therapeutic plasma exchange were all unsuccessful. Interestingly, complement inhibition with Eculizumab as rescue approach led to a rapid clinical and laboratory improvement and the patients were discharged with normalized organ functions at Day 36. Conclusion: The aetiology of cardiogenic shock observed in this patient cannot simply be explained by his focal and chronic coronary findings. Although viral myocarditis was not formally excluded, both the clinical features of TMA and the rapid resolution of all clinical signs and symptoms after pharmacological complement inhibition suggest a SARS-CoV-2-driven microangiopathic origin of heart failure.
Language	English
Publishing date	2021-09-28
Publishing country	England
Document type	Case Reports
ISSN	2514-2119
ISSN (online)	2514-2119
DOI	10.1093/ehjcr/ytab386
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Article ; Online: Better by design: What to expect from novel CAR-engineered cell therapies?

Luginbuehl, Vera / Abraham, Eytan / Kovar, Karin / Flaaten, Richard / Müller, Antonia M S

Biotechnology advances

2022 Volume 58, Page(s) 107917

Abstract	Chimeric antigen receptor (CAR) technology, and CAR-T cells in particular, have emerged as a new and powerful tool in cancer immunotherapy since demonstrating efficacy against several hematological malignancies. However, despite encouraging clinical results of CAR-T cell therapy products, a significant proportion of patients do not achieve satisfactory responses, or relapse. In addition, CAR-T cell applications to solid tumors is still limited due to the tumor microenvironment and lack of specifically targetable tumor antigens. All current products on the market, as well as most investigational CAR-T cell therapies, are autologous, using the patient's own peripheral blood mononuclear cells as starting material to manufacture a patient-specific batch. Alternative cell sources are, therefore, under investigation (e.g. allogeneic cells from an at least partially human leukocyte antigen (HLA)-matched healthy donor, universal "third-party" cells from a non-HLA-matched donor, cord blood-derived cells, immortalized cell lines or cells differentiated from induced pluripotent stem cells). However, genetic modifications of CAR-engineered cells, bioprocesses used to expand cells, and improved supply chains are still complex and costly. To overcome drawbacks associated with CAR-T technologies, novel CAR designs have been used to genetically engineer cells derived from alpha beta (αβ) T cells, other immune cells such as natural killer (NK) cells, gamma delta (γδ) T cells, macrophages or dendritic cells. This review endeavours to trigger ideas on the next generation of CAR-engineered cell therapies beyond CAR-T cells and, thus, will enable effective, safe and affordable therapies for clinical management of cancer. To achieve this, we present a multidisciplinary overview, addressing a wide range of critical aspects: CAR design, development and manufacturing technologies, pharmacological concepts and clinical applications of CAR-engineered cell therapies. Each of these fields employs a large number of ground-breaking scientific advances, where coordinated and complex process and product development occur at their interfaces.
MeSH term(s)	Humans ; Immunotherapy, Adoptive ; Leukocytes, Mononuclear ; Neoplasms/therapy ; Receptors, Chimeric Antigen/genetics ; T-Lymphocytes ; Tumor Microenvironment
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2022-02-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	47165-3
ISSN	1873-1899 ; 0734-9750
ISSN (online)	1873-1899
ISSN	0734-9750
DOI	10.1016/j.biotechadv.2022.107917
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Article ; Online: The stepchild in myeloma treatments: is allogeneic transplantation not so bad after all?

Müller, Antonia M S / Kumar, Shaji K / Bruno, Benedetto

Haematologica

2019 Volume 104, Issue 2, Page(s) 222–225

MeSH term(s)	Graft vs Host Disease/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Multiple Myeloma/diagnosis ; Multiple Myeloma/mortality ; Multiple Myeloma/therapy ; Transplantation Conditioning ; Transplantation, Homologous ; Treatment Outcome
Language	English
Publishing date	2019-01-21
Publishing country	Italy
Document type	Editorial
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2018.206987
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Article ; Online: Elimination of Herpes Simplex Virus-2 and Epstein-Barr Virus With Seraph 100 Microbind Affinity Blood Filter and Therapeutic Plasma Exchange: An Explorative Study in a Patient With Acute Liver Failure.

Andermatt, Rea / Bloemberg, Guido V / Ganter, Christoph C / Mueller, Nicolas J / Mueller, Antonia M S / Muellhaupt, Beat / Kielstein, Jan T / David, Sascha

Critical care explorations

2022 Volume 4, Issue 8, Page(s) e0745

Abstract: Herpes simplex virus (HSV)-2 is a rare cause of hepatitis that can lead to acute liver failure (ALF) and often death. The earlier the initiation of acyclovir treatment the better the survival. With regard to ALF, controlled randomized data support the ... ...

Abstract	Herpes simplex virus (HSV)-2 is a rare cause of hepatitis that can lead to acute liver failure (ALF) and often death. The earlier the initiation of acyclovir treatment the better the survival. With regard to ALF, controlled randomized data support the use of therapeutic plasma exchange (TPE) both as bridge to recovery or transplantation-possibly by modulating the systemic inflammatory response and by replacing coagulation factors. Seraph 100 Microbind Affinity Blood Filter (Seraph; Ex Thera Medical, Martinez, CA), a novel extracorporeal adsorption device, removes living pathogens by binding to a heparin-coated surface was shown to efficiently clear HSV-2 particles in vitro. Here, we tested the combination of Seraph with TPE to reduce a massive HSV-2 viral load to reach a situation in that liver transplantation would be feasible. Design: Explorative study. Setting: Academic tertiary care transplant center. Patient: Single patient with HSV-2-induced ALF. Interventions: TPE + Seraph 100 Microbind Affinity Blood Filter. Measurements and main results: We report Seraph clearance data of HSV-2 and of Epstein-Barr virus (EBV) in vivo as well as total viral elimination by TPE. Genome copies/mL of HSV-2 and EBV in EDTA plasma were measured by polymerase chain reaction every 60 minutes over 6 hours after starting Seraph both systemically and post adsorber. Also, HSV-2 and EBV were quantified before and after TPE and in the removed apheresis plasma. We found a total elimination of 1.81 × e Conclusions: TPE was able to remove circulating HSV-2 copies by 25% and EBV copies by 40% from the blood. On the other hand, clearance of HSV-2 by Seraph was clinically irrelevant, but Seraph seemed to be far more effective of removing EBV, implicating a possible use in EBV-associated pathologies, but this requires further study.
Language	English
Publishing date	2022-08-11
Publishing country	United States
Document type	Journal Article
ISSN	2639-8028
ISSN (online)	2639-8028
DOI	10.1097/CCE.0000000000000745
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Article ; Online: Dynamics of T cell repertoire renewal following autologous hematopoietic stem cell transplantation in multiple sclerosis.

Ruder, Josefine / Docampo, María José / Rex, Jordan / Obahor, Simon / Naghavian, Reza / Müller, Antonia M S / Schanz, Urs / Jelcic, Ilijas / Martin, Roland

Science translational medicine

2022 Volume 14, Issue 669, Page(s) eabq1693

Abstract: Autologous hematopoietic stem cell transplantation (aHSCT) is a highly effective treatment of multiple sclerosis (MS). It depletes autoreactive cells and subsequently renews adaptive immune cells. The possible proinflammatory potential of surviving T ... ...

Abstract	Autologous hematopoietic stem cell transplantation (aHSCT) is a highly effective treatment of multiple sclerosis (MS). It depletes autoreactive cells and subsequently renews adaptive immune cells. The possible proinflammatory potential of surviving T cells early after aHSCT has not been studied. Here, we examined the dynamics of new and surviving T cells in 27 patients after aHSCT by multidimensional flow cytometry, T cell receptor (TCR) sequencing, specificity testing, telomere length profiling, and HLA genotyping. Early after aHSCT, naïve T cells are barely detectable, whereas effector memory (EM) T cells quickly reconstitute to pre-aHSCT values. EM CD4
MeSH term(s)	Humans ; Multiple Sclerosis/therapy ; Transplantation, Autologous/methods ; Hematopoietic Stem Cell Transplantation/methods ; Lymphocyte Count
Language	English
Publishing date	2022-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abq1693
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Article ; Online: Resource utilization for chimeric antigen receptor T cell therapy versus autologous hematopoietic cell transplantation in patients with B cell lymphoma.

Ring, Alexander / Grob, Björn / Aerts, Erik / Ritter, Katharina / Volbracht, Jörk / Schär, Bettina / Greiling, Michael / Müller, Antonia M S

Annals of hematology

2022 Volume 101, Issue 8, Page(s) 1755–1767

Abstract: CD19-directed chimeric antigen receptor T cells (CAR-T) have emerged as a highly efficacious treatment for patients with relapsed/refractory (r/r) B cell lymphoma (BCL). The value of CAR-T for these patients is indisputable, but one-off production costs ... ...

Abstract	CD19-directed chimeric antigen receptor T cells (CAR-T) have emerged as a highly efficacious treatment for patients with relapsed/refractory (r/r) B cell lymphoma (BCL). The value of CAR-T for these patients is indisputable, but one-off production costs are high, and little is known about the ancillary resource consumption associated with CAR-T treatment. Here, we compared the resource use and costs of CAR-T treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for patients with r/r BCL. Standard operating procedures were used to develop a process model in ClipMed
MeSH term(s)	Antigens, CD19 ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, B-Cell/drug therapy ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; Transplantation, Autologous/methods
Chemical Substances	Antigens, CD19 ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen
Language	English
Publishing date	2022-06-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-022-04881-0
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Article ; Online: Introducing innovative cellular therapies into the clinic: a 2-year retrospective experience of a chimeric antigen receptor T-cell programme at a single centre in Switzerland.

Stolz, Sebastian / Roncador, Marco / Rösler, Wiebke / Zenz, Thorsten / Manz, Markus G / Müller, Antonia M S / Widmer, Corinne C

Swiss medical weekly

2022 Volume 152, Page(s) w30186

Abstract: Aim of the study: Chimeric antigen receptor T (CAR-T) cells are a powerful form of immune-cell therapy for patients with relapsed/refractory B-cell lymphoma and acute B lymphoblastic leukaemia. CAR-T cells have been commercially available in Switzerland ...

Abstract	Aim of the study: Chimeric antigen receptor T (CAR-T) cells are a powerful form of immune-cell therapy for patients with relapsed/refractory B-cell lymphoma and acute B lymphoblastic leukaemia. CAR-T cells have been commercially available in Switzerland since 2018. Because of the complexity and costs of this treatment it is critical to review patient outcomes in real-world settings, to examine whether the promising results from pivotal trials can be reproduced and to identify clinical parameters that determine their efficacy. Methods: Here we present results of a retrospective study analysing outcomes of patients treated with CAR-T cells in a single academic centre in Switzerland during the first two years after commercial approval (BASEC-No. 2020-02271). Cytokine release syndrome (CRS), immune-cell associated neurotoxicity syndrome (ICANS), responses to treatment, ancillary laboratory studies and administrative specifics of CAR-T treatment were examined and are discussed. Results: From October 2018 to August 2020 CAR-T cell therapy was evaluated in 34 patients, mostly with relapsed/refractory aggressive B-cell lymphoma (87% had refractory disease). Thirty-one patients underwent leukapheresis. Three of 31 patients (9.6%) died of rapid disease progression before the CAR-T cell product was delivered, two patients were enrolled into a clinical trial, three patients were not given CAR-T cells for other reasons. Ultimately, 23 patients were infused with a commercial CAR-T cell product and included in this analysis. Fourteen (61%) patients received bridging therapy while waiting for a median of 41 days (range 31-62) for delivery of the CAR-T cell product. Toxicity and severe side effects were rare (CRS >3 in 13%, ICANS > grade 3 in 10% of patients), manageable and resolved completely thereafter. The best overall response rate was 65%, with complete responses in 38% of lymphoma patients. At 12 months postinfusion, 61% of patients were alive and 35% progression free. With a median follow-up of 14 months, 13/23 (56%) patients were alive at the time of writing. Conclusion: CAR-T cell therapy proved to be safe and manageable under adequate hospital conditions. Outcomes resemble results from pivotal trials. The majority of patients was heavily pretreated and refractory at the time of CAR-T cell infusion. Patient selection, time point of leukapheresis, bridging strategies and timing of CAR-T cell infusion may be critical to further improve outcomes.
MeSH term(s)	Cytokine Release Syndrome ; Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Lymphoma, B-Cell/drug therapy ; Neoplasm Recurrence, Local/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Receptors, Chimeric Antigen/therapeutic use ; Retrospective Studies ; Switzerland
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2022-06-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2036179-8
ISSN	1424-3997 ; 1424-7860
ISSN (online)	1424-3997
ISSN	1424-7860
DOI	10.4414/smw.2022.w30186
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