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Article ; Online: Cellular Immunotherapy-Highlights from TCT 2021.

Reshef, Ran / Muranski, Pawel / Miller, Jeffrey S

2021 Volume 27, Issue 7, Page(s) 527–532

MeSH term(s)	Immunotherapy
Language	English
Publishing date	2021-04-26
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2021.04.015
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Article ; Online: An easy way to make a good anti-tumor chimeric antigen receptor T cell?

Muranski, Pawel

Cytotherapy

2014 Volume 16, Issue 5, Page(s) 577–578

MeSH term(s)	Animals ; Humans ; Immunotherapy, Adoptive/methods ; Leukemia/therapy
Language	English
Publishing date	2014-05
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2014.03.003
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Article: Cellular therapy for the treatment of solid tumors.

Grimes, Joseph M / Carvajal, Richard D / Muranski, Pawel

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

2021 Volume 60, Issue 1, Page(s) 103056

Abstract: Adoptive cellular therapy (ACT) is a form of cancer immunotherapy in which lymphocytes are removed from patient blood or tumor samples, expanded and/or genetically modified to improve tumor-fighting capabilities, and infused back into the patient. The ... ...

Abstract	Adoptive cellular therapy (ACT) is a form of cancer immunotherapy in which lymphocytes are removed from patient blood or tumor samples, expanded and/or genetically modified to improve tumor-fighting capabilities, and infused back into the patient. The main forms of ACT include tumor infiltrating lymphocytes (TILs), engineered T cell receptor (TCR) T cells, and chimeric antigen receptor (CAR) T cells. While ACT has had success in hematological malignancies, particularly in B cell lymphomas targeted with CAR T cells, these favorable outcomes have yet to be replicated in solid tumors. Appropriate solid tumor target antigens are difficult to identify for ACT. Trafficking to tumor sites and infiltrating solid tumor burdens remains a problem for ACT cells. Persistence of ACT cells, which is important in creating a durable response, is also a major challenge, partly attributed to the formidable microtumor environment conditions. The costly and time-intensive manufacturing process for ACT is also an obstacle to widespread adoption. In this review, we discuss the challenges of ACT therapy in the treatment of solid tumors and explore the ongoing efforts to improve this immunotherapy approach in non-hematological malignancies.
MeSH term(s)	Cell- and Tissue-Based Therapy/methods ; Humans ; Neoplasms/pathology ; Neoplasms/therapy ; T-Lymphocytes/immunology
Language	English
Publishing date	2021-01-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2046795-3
ISSN	1878-1683 ; 1473-0502
ISSN (online)	1878-1683
ISSN	1473-0502
DOI	10.1016/j.transci.2021.103056
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Article ; Online: Rapid video-based deep learning of cognate versus non-cognate T cell-dendritic cell interactions.

Anandakumaran, Priya N / Ayers, Abigail G / Muranski, Pawel / Creusot, Remi J / Sia, Samuel K

Scientific reports

2022 Volume 12, Issue 1, Page(s) 559

Abstract: Identification of cognate interactions between antigen-specific T cells and dendritic cells (DCs) is essential to understanding immunity and tolerance, and for developing therapies for cancer and autoimmune diseases. Conventional techniques for selecting ...

Abstract	Identification of cognate interactions between antigen-specific T cells and dendritic cells (DCs) is essential to understanding immunity and tolerance, and for developing therapies for cancer and autoimmune diseases. Conventional techniques for selecting antigen-specific T cells are time-consuming and limited to pre-defined antigenic peptide sequences. Here, we demonstrate the ability to use deep learning to rapidly classify videos of antigen-specific CD8
MeSH term(s)	CD8-Positive T-Lymphocytes
Language	English
Publishing date	2022-01-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-04286-5
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Article ; Online: Case Report: Kinetics and durability of humoral and cellular response of SARS-CoV-2 messenger RNA vaccine in a lung and kidney transplant recipient.

Long, James / Soni, Mithil / Muranski, Pawel / Miller, Maureen J / Conry-Cantilena, Cathleen / De Giorgi, Valeria

Frontiers in immunology

2023 Volume 14, Page(s) 1207638

Abstract: We present a case report of a 63-year-old female health care worker who is 15 years status post double lung transplant and six years status post living related donor kidney transplant who is healthy on a chronic immunosuppression regimen including ... ...

Abstract	We present a case report of a 63-year-old female health care worker who is 15 years status post double lung transplant and six years status post living related donor kidney transplant who is healthy on a chronic immunosuppression regimen including prednisone, mycophenolate, and tacrolimus who received the SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech BNT162b2) primary series and had poor initial humoral response to the COVID-19 mRNA vaccine, then demonstrated a robust, sustained immune response against S1 and S2 antigens for over seven months after receiving the recommended vaccine doses, including booster dose, without developing COVID-19 or other serious adverse events. Her immune response to vaccination indicates effective formation of anti-spike T cell memory despite chronic immunosuppression. This case report provides a comprehensive characterization of her immune response to this SARS-CoV-2 vaccination series. As vaccine effectiveness data is updated, and as better understanding of immune response including hybrid immunity emerges, these findings may reassure that recipients of SOTs may be capable of durable immune responses to emerging variants of SARS-CoV-2.
MeSH term(s)	Female ; Humans ; Middle Aged ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; Kidney Transplantation/adverse effects ; Kinetics ; Lung ; SARS-CoV-2
Chemical Substances	BNT162 Vaccine ; COVID-19 Vaccines
Language	English
Publishing date	2023-07-03
Publishing country	Switzerland
Document type	Case Reports ; Research Support, N.I.H., Intramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1207638
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Article ; Online: T cell therapies for human polyomavirus diseases.

Davies, Sarah I / Muranski, Pawel

Cytotherapy

2017

Abstract: Rapid restoration of virus-specific T immunity via adoptive transfer of ex vivo generated T cells has been proven as a powerful therapy for patients with advanced cancers and refractory viral infections such as cytomegalovirus (CMV) and Epstein-Barr ... ...

Abstract	Rapid restoration of virus-specific T immunity via adoptive transfer of ex vivo generated T cells has been proven as a powerful therapy for patients with advanced cancers and refractory viral infections such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). BK virus (BKV), John Cunningham virus (JCV), and Merkel cell carcinoma virus (MCV) are the members of the rapidly growing human polyomavirus (hPyV) family that commonly infects most healthy humans. These viruses have a clearly established potential for causing severe end-organ damage or malignant transformation, especially in individuals with weakened immunity who are unable to mount or regain endogenous T-cell responses as a result of underlying leukemia or iatrogenic immunosuppression in autoimmunity, bone marrow and solid organ transplant settings. Here we will discuss recent advances in using T-cell-based immunotherapies to save patients suffering from PyV-associated diseases including hemorrhagic cystitis, BKV virus-associated nephropathy, and JC-associated progressive multifocal leukoencephalopathy (PML). We will also review progress in the understanding of Merkel cell carcinoma (MCC) as a virally driven tumor that is amenable to immune intervention and can be targeted with adoptively transferred T cells specific for viral oncoproteins.
Language	English
Publishing date	2017-09-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2017.08.011
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Zs.A 5601: Show issues

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Article ; Online: Rapid video-based deep learning of cognate versus non-cognate T cell-dendritic cell interactions

Priya N. Anandakumaran / Abigail G. Ayers / Pawel Muranski / Remi J. Creusot / Samuel K. Sia

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 10

Abstract: Abstract Identification of cognate interactions between antigen-specific T cells and dendritic cells (DCs) is essential to understanding immunity and tolerance, and for developing therapies for cancer and autoimmune diseases. Conventional techniques for ... ...

Abstract	Abstract Identification of cognate interactions between antigen-specific T cells and dendritic cells (DCs) is essential to understanding immunity and tolerance, and for developing therapies for cancer and autoimmune diseases. Conventional techniques for selecting antigen-specific T cells are time-consuming and limited to pre-defined antigenic peptide sequences. Here, we demonstrate the ability to use deep learning to rapidly classify videos of antigen-specific CD8+ T cells. The trained model distinguishes distinct interaction dynamics (in motility and morphology) between cognate and non-cognate T cells and DCs over 20 to 80 min. The model classified high affinity antigen-specific CD8+ T cells from OT-I mice with an area under the curve (AUC) of 0.91, and generalized well to other types of high and low affinity CD8+ T cells. The classification accuracy achieved by the model was consistently higher than simple image analysis techniques, and conventional metrics used to differentiate between cognate and non-cognate T cells, such as speed. Also, we demonstrated that experimental addition of anti-CD40 antibodies improved model prediction. Overall, this method demonstrates the potential of video-based deep learning to rapidly classify cognate T cell-DC interactions, which may also be potentially integrated into high-throughput methods for selecting antigen-specific T cells in the future.
Keywords	Medicine ; R ; Science ; Q
Subject code	004
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Restoring antiviral immunity with adoptive transfer of ex-vivo generated T cells.

Migliori, Edoardo / Chang, Mark / Muranski, Pawel

Current opinion in hematology

2018 Volume 25, Issue 6, Page(s) 486–493

Abstract: Purpose of review: Latent viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus (ADV) often reactivate in immunocompromised patients, contributing to poor clinical outcomes. A rapid reconstitution of antiviral responses via ... ...

Abstract	Purpose of review: Latent viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus (ADV) often reactivate in immunocompromised patients, contributing to poor clinical outcomes. A rapid reconstitution of antiviral responses via adoptive transfer of virus-specific T cells (VSTs) can prevent or eradicate even refractory infections. Here, we evaluate this strategy and the associated methodological, manufacturing and clinical advances. Recent findings: From the early pioneering but cumbersome efforts to isolate CMV-specific T cell clones, new approaches and techniques have been developed to provide quicker, safer and broader-aimed ex-vivo antigen-specific cells. New manufacturing strategies, such as the use of G-Rex flasks or 'priming' with a library of overlapping viral peptides, allow for culturing greater numbers of cells that could be patient-specific or stored in cell banks for off-the-shelf applications. Rapid isolation of T cells using major histocompatibility complex tetramer or cytokine capture approaches, or genetic reprogramming of cells to target viral antigens can accelerate the generation of potent cellular products. Summary: Advances in the ex-vivo generation of VSTs in academic medical centres and as off-the-shelf blood bank-based or commercially produced reagents are likely to result in broader accessibility and possible manufacturing cost reduction of these cell products, and will open new therapeutic prospects for vulnerable and critically ill immunocompromised patients.
MeSH term(s)	Humans ; Adoptive Transfer ; Cytomegalovirus/drug effects ; Cytomegalovirus/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/virology ; Virus Diseases/immunology
Keywords	covid19
Language	English
Publishing date	2018-10-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000461
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Article: The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses.

Soni, Mithil / Migliori, Edoardo / Fu, Jianing / Assal, Amer / Chan, Hei Ton / Pan, Jian / Khatiwada, Prabesh / Ciubotariu, Rodica / May, Michael S / Pereira, Marcus / De Giorgi, Valeria / Sykes, Megan / Mapara, Markus Y / Muranski, Pawel

bioRxiv : the preprint server for biology

2023

Abstract: T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19). Therefore, T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for immunocompromised patients. Pre-existing T ... ...

Abstract	T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19). Therefore, T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of "common cold". In turn, SARS-CoV2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and β-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV2 spike-specific T cells reliably recognized most SARS-CoV2 variants, however cross-reactivity against the
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.03.519511
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Article ; Online: The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses.

Soni, Mithil K / Migliori, Edoardo / Fu, Jianing / Assal, Amer / Chan, Hei Ton / Pan, Jian / Khatiwada, Prabesh / Ciubotariu, Rodica / May, Michael S / Pereira, Marcus R / De Giorgi, Valeria / Sykes, Megan / Mapara, Markus Y / Muranski, Pawel J

Frontiers in immunology

2023 Volume 14, Page(s) 1212203

Abstract: T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T ... ...

Abstract	T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of "common cold". In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and β-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; RNA, Viral ; Coronavirus OC43, Human
Chemical Substances	RNA, Viral
Language	English
Publishing date	2023-10-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1212203
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