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Article ; Online: Genome-edited allogeneic donor "universal" chimeric antigen receptor T cells.

Qasim, Waseem

2022 Volume 141, Issue 8, Page(s) 835–845

Abstract: αβ T cell receptor (TCRαβ) T cells modified to express chimeric antigen receptors (CAR), are now available as authorized therapies for certain B-cell malignancies. However the process of autologous harvest and generation of patient-specific products is ... ...

Abstract	αβ T cell receptor (TCRαβ) T cells modified to express chimeric antigen receptors (CAR), are now available as authorized therapies for certain B-cell malignancies. However the process of autologous harvest and generation of patient-specific products is costly, with complex logistics and infrastructure requirements. Premanufactured banks of allogeneic donor-derived CAR T cells could help widen applicability if the challenges of HLA-mismatched T-cell therapy can be addressed. Genome editing is being applied to overcome allogeneic barriers, most notably, by disrupting TCRαβ to prevent graft-versus-host disease, and multiple competing editing technologies, including CRISPR/Cas9 and base editing, have reached clinical phase testing. Improvements in accuracy and efficiency have unlocked applications for a wider range of blood malignancies, with multiplexed editing incorporated to target HLA molecules, shared antigens and checkpoint pathways. Clinical trials will help establish safety profiles and determine the durability of responses as well as the role of consolidation with allogeneic transplantation.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Receptors, Antigen, T-Cell/genetics ; T-Lymphocytes ; Neoplasms/therapy ; Gene Editing ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Hematopoietic Stem Cell Transplantation
Chemical Substances	Receptors, Chimeric Antigen ; Receptors, Antigen, T-Cell ; Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022016204
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Article ; Online: Genome editing of therapeutic T cells.

Qasim, Waseem

Gene and genome editing

2021 Volume 2, Page(s) None

Abstract: The potential of engineered TCRαβ T cells as potent mediators of leukemic clearance has been demonstrated in clinical trials, and authorised therapies are being deployed against B cell malignancies in particular. While most applications have relied on ... ...

Abstract	The potential of engineered TCRαβ T cells as potent mediators of leukemic clearance has been demonstrated in clinical trials, and authorised therapies are being deployed against B cell malignancies in particular. While most applications have relied on harvest and manipulation of autologous lymphocytes, the emerging application of genome editing technology has demonstrated that allogeneic TCRαβ cells can be engineered to overcome Human Leukocyte Antigen (HLA) barriers and provides a route to more cost effective and widely accessible 'off-the-shelf' therapies. Genome editing also offers the prospect of addressing other hurdles such as shared-antigen expression and has been applied to direct site-specific transgene integration, for improved transcriptional regulation and function.
Language	English
Publishing date	2021-11-25
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2666-3880
ISSN (online)	2666-3880
DOI	10.1016/j.ggedit.2021.100010
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Article: Emerging therapeutic applications of CRISPR genome editing.

Qasim, Waseem

Emerging topics in life sciences

2021 Volume 3, Issue 3, Page(s) 257–260

Abstract: The rapid evolution of tools for genome editing has created a dizzying array of possibilities for novel therapeutic strategies, even though to date only a handful of clinical applications have been realised. Proof-of-concept demonstrations of targeted ... ...

Abstract	The rapid evolution of tools for genome editing has created a dizzying array of possibilities for novel therapeutic strategies, even though to date only a handful of clinical applications have been realised. Proof-of-concept demonstrations of targeted genome modification in vitro and in small animal models of inherited single gene disorders have to be translated into effective therapies. Interest has naturally gravitated towards opportunities for collection, ex vivo modification and return of blood, immune and stem cells. Initial applications designed to modify T cells to protect against HIV or to confer potent anti-leukaemic effects have reached clinical phase, and further applications to modify blood stem cells are close to being applied. There are generic considerations of safety, on- and off-target effects and possible genotoxicity as well as issues relating to more sophisticated systemic approaches where niche occupation and host immunity become relevant. Such issues will be likely addressed over time, with carefully designed clinical trials required to determine therapeutic risks and benefits.
Language	English
Publishing date	2021-03-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2882721-1
ISSN	2397-8554 ; 2397-8554 ; 2397-8562
ISSN (online)	2397-8554
ISSN	2397-8554 ; 2397-8562
DOI	10.1042/ETLS20190010
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Article ; Online: Allogeneic CAR T cell therapies for leukemia.

Qasim, Waseem

American journal of hematology

2019 Volume 94, Issue S1, Page(s) S50–S54

Abstract: Allogeneic chimeric antigen receptor T (CAR T) cells can offer advantages over autologous T cell therapies, including the availability of "fit" cells for production, and elimination of risks associated with inadvertent transduction of leukemic blasts. ... ...

Abstract	Allogeneic chimeric antigen receptor T (CAR T) cells can offer advantages over autologous T cell therapies, including the availability of "fit" cells for production, and elimination of risks associated with inadvertent transduction of leukemic blasts. However, allogeneic T cell therapies must address HLA barriers and conventionally rely on the availability of a suitable HLA-matched donor if graft-vs-host-disease and rejection effects are to be avoided. More recently, the incorporation of additional genome editing manipulations, to disrupt T cell receptor expression and address other critical pathways have been explored. Clinical trials are underway investigating non-HLA matched T cells expressing anti-CD19 CARs for the treatment of B cell acute lymphoblastic leukemia (B-ALL) and anti-CD123 CAR for acute myeloid leukemia (AML). Such approaches continue to be refined and improved to widen accessibility and reduce the cost of T cell therapies for a wider range of conditions.
MeSH term(s)	Humans ; Immunotherapy, Adoptive/methods ; Leukemia/therapy ; Leukemia, Myeloid, Acute/therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Receptors, Chimeric Antigen/immunology ; Receptors, Chimeric Antigen/therapeutic use ; Transplantation, Homologous
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2019-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.25399
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Article ; Online: Genome-Edited T Cell Therapies.

Ottaviano, Giorgio / Qasim, Waseem

Hematology/oncology clinics of North America

2022 Volume 36, Issue 4, Page(s) 729–744

Abstract: Chimeric antigen receptor (CAR) T-cells are widely being investigated against malignancies, and allogeneic 'universal donor' CAR-T cells offer the possibility of widened access to pre-manufactured, off-the-shelf therapies. Different genome-editing ... ...

Abstract	Chimeric antigen receptor (CAR) T-cells are widely being investigated against malignancies, and allogeneic 'universal donor' CAR-T cells offer the possibility of widened access to pre-manufactured, off-the-shelf therapies. Different genome-editing platforms have been used to address human leukocyte antigen (HLA) barriers to generate universal CAR-T cell therapy and early applications have been reported in children and adults against B cell malignancies. Recently developed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based systems and related technologies offer the prospect of enhanced cellular immunotherapies for a wider range of hematological malignancies.
MeSH term(s)	CRISPR-Cas Systems ; Child ; Gene Editing/methods ; Humans ; Immunotherapy, Adoptive/methods ; Neoplasms/therapy ; T-Lymphocytes
Language	English
Publishing date	2022-06-27
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	93115-9
ISSN	1558-1977 ; 0889-8588
ISSN (online)	1558-1977
ISSN	0889-8588
DOI	10.1016/j.hoc.2022.03.006
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Article: Simulation, Fabrication and Microfiltration Using Dual Anodic Aluminum Oxide Membrane.

Qasim, Faheem / Ashraf, Muhammad Waseem / Tayyaba, Shahzadi / Tariq, Muhammad Imran / Herrera-May, Agustín L

Membranes

2023 Volume 13, Issue 10

Abstract: Microfluidic devices have gained subsequent attention due to their controlled manipulation of fluid for various biomedical applications. These devices can be used to study the behavior of fluid under several micrometer ranges within the channel. The ... ...

Abstract	Microfluidic devices have gained subsequent attention due to their controlled manipulation of fluid for various biomedical applications. These devices can be used to study the behavior of fluid under several micrometer ranges within the channel. The major applications are the filtration of fluid, blood filtration and bio-medical analysis. For the filtration of water, as well as other liquids, the micro-filtration based microfluidic devices are considered as potential candidates to fulfill the desired conditions and requirements. The micro pore membrane can be designed and fabricated in such a way that it maximizes the removal of impurities from fluid. The low-cost micro-filtration method has been reported to provide clean fluid for biomedical applications and other purposes. In the work, anodic-aluminum-oxide-based membranes have been fabricated with different pore sizes ranging from 70 to 500 nm. A soft computing technique like fuzzy logic has been used to estimate the filtration parameters. Then, the finite-element-based analysis system software has been used to study the fluid flow through the double membrane. Then, filtration is performed by using a dual membrane and the clogging of the membrane has been studied after different filtration cycles using characterization like a scanning electron microscope. The filtration has been done to purify the contaminated fluid which has impurities like bacteria and protozoans. The membranes have been tested after each cycle to verify the results. The decrease in permeance with respect to the increase in the velocity of the fluid and the permeate volume per unit clearly depicts the removal of containments from the fluid after four and eight cycles of filtration. The results clearly show that the filtration efficiency can be improved by increasing the number of cycles and adding a dual membrane in the micro-fluidic device. The results show the potential of dual anodic aluminum oxide membranes for the effective filtration of fluids for biomedical applications, thereby offering a promising solution to address current challenges.
Language	English
Publishing date	2023-10-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2614641-1
ISSN	2077-0375
ISSN	2077-0375
DOI	10.3390/membranes13100825
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Article ; Online: Genome Editing in Engineered T Cells for Cancer Immunotherapy.

Bonini, Chiara / Chapuis, Aude G / Hudecek, Michael / Guedan, Sonia / Magnani, Chiara / Qasim, Waseem

Human gene therapy

2023 Volume 34, Issue 17-18, Page(s) 853–869

Abstract: Advanced gene transfer technologies and profound immunological insights have enabled substantial increases in the efficacy of anticancer adoptive cellular therapy (ACT). In recent years, the U.S. Food and Drug Administration and European Medicines Agency ...

Abstract	Advanced gene transfer technologies and profound immunological insights have enabled substantial increases in the efficacy of anticancer adoptive cellular therapy (ACT). In recent years, the U.S. Food and Drug Administration and European Medicines Agency have approved six engineered T cell therapeutic products, all chimeric antigen receptor-engineered T cells directed against B cell malignancies. Despite encouraging clinical results, engineered T cell therapy is still constrained by challenges, which could be addressed by genome editing. As RNA-guided Clustered Regularly Interspaced Short Palindromic Repeats technology passes its 10-year anniversary, we review emerging applications of genome editing approaches designed to (1) overcome resistance to therapy, including cancer immune evasion mechanisms; (2) avoid unwanted immune reactions related to allogeneic T cell products; (3) increase fitness, expansion capacity, persistence, and potency of engineered T cells, while preserving their safety profile; and (4) improve the ability of therapeutic cells to resist immunosuppressive signals active in the tumor microenvironment. Overall, these innovative approaches should widen the safe and effective use of ACT to larger number of patients affected by cancer.
MeSH term(s)	United States ; Humans ; Gene Editing ; T-Lymphocytes ; Immunotherapy ; Anniversaries and Special Events ; B-Lymphocytes ; Neoplasms/genetics ; Neoplasms/therapy
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2023.128
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Zs.A 2988: Show issues

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Article ; Online: Ground motion hazard of the China–Pakistan Economic Corridor (CPEC) routes in Pakistan

Qasim Ur Rehman / Muhammad Waseem / Waqas Ahmed / Ihtisham Islam / Hammad Tariq Janjuhah / George Kontakiotis

Progress in Earth and Planetary Science, Vol 10, Iss 1, Pp 1-

2023 Volume 31

Abstract: Abstract Pakistan has seen a burst of infrastructure development recently due to the increased connection between Asia and East Europe. The China–Pakistan Economic Corridor is a project between China and Pakistan aimed to improve the regional ... ...

Abstract	Abstract Pakistan has seen a burst of infrastructure development recently due to the increased connection between Asia and East Europe. The China–Pakistan Economic Corridor is a project between China and Pakistan aimed to improve the regional infrastructure that would ultimately enhance the connection between Asia and Eastern Europe. However, the active tectonics of Pakistan could put this infrastructure at risk if it is not built to the highest hazard prevention standard. This study reports the ground motion hazard by using the probabilistic seismic hazard assessment approach and the areal seismic source model. The seismic hazard maps of the China–Pakistan Economic Corridor in Pakistan are derived using the Cornell–McGuire (1968–1976) approach, which takes into account all earthquakes (25AD-2020) that occurred in Pakistan and nearby regions, the newest ground motion prediction equations, and an updated seismotectonic source model of Pakistan. The final ground motion intensities are attained as peak ground acceleration and 5% damped spectral acceleration at T = 0.2 s and 1.0 s for 475- and 2475-year return periods (estimated for bedrock site conditions). The results are displayed as color-coded maps that represent the amplitude deviation of ground motion. From the spatial evaluation of the maps, a peak ground acceleration value of 0.40–0.52 g for the 475-year return period and a spectral acceleration (0.2 s) value of 1.66–2.13 g for 2475-year return period are mostly observed on the northern and western routes. The central and eastern routes are mostly characterized by a peak ground acceleration value of 0.22–0.24 g for the 475-year return period and a spectral acceleration (0.2 s) value of 0.95–1.13 g due to diffused seismicity and lower number of faults in this region. The ground motion intensity values obtained in this study can be utilized for the seismic design of all kinds of infrastructure and bridges along the CPEC routes in accordance with the Building Code of Pakistan, the International Building codes, ...
Keywords	Probabilistic seismic hazard ; Seismic design ; Areal source model ; PGA and SA ; CPEC route ; Geography. Anthropology. Recreation ; G ; Geology ; QE1-996.5
Subject code	950
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
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Article: Tumor Lysis Syndrome in the Chronic Phase of Chronic Myeloid Leukemia Following COVID-19 Infection: A Case Report.

Waseem Hajjar, Adnan Humam / Abbarh, Shahem / Al-Mashdali, Abdulrahman / Alshurafa, Awni / Abu-Tineh, Mohammad / Qasim, Hana / Ahmed, Khalid / Yassin, Mohamed A

Cureus

2022 Volume 14, Issue 4, Page(s) e24386

Abstract: Tumor lysis syndrome (TLS) is a hematological emergency. This syndrome is characterized by metabolic derangements such as hyperkalemia and hypocalcemia, which result from rapid lysis of cells, especially rapidly growing tumors, after the initiation of ... ...

Abstract	Tumor lysis syndrome (TLS) is a hematological emergency. This syndrome is characterized by metabolic derangements such as hyperkalemia and hypocalcemia, which result from rapid lysis of cells, especially rapidly growing tumors, after the initiation of chemotherapy. It is rarely seen in chronic myeloid leukemia (CML) and has not been previously reported to be triggered by coronavirus disease 2019 (COVID-19) infection. We report a case of a 45-year-old male, a known case of CML in the chronic phase, who presented with fatigue and abdominal pain for four days. Initial laboratory results were consistent with leukocytosis and positive COVID-19 antigen. The patient was started on intravenous fluids and hydroxyurea; however, over the next few days, he deteriorated quickly and developed oliguric acute kidney injury (AKI) with electrolyte disturbance consistent with TLS. The patient was shifted to the intensive care unit and underwent one sustained low-efficiency dialysis (SLED) session and received rasburicase. Over the next few days, the patient started to improve and was discharged in good shape. Although CML rarely presents with TLS, physicians should monitor their patients closely, especially those who have concurrent COVID-19 infection, as this condition may result in lethal sequelae such as AKI, severe arrhythmias, and multiorgan failure. Additionally, early detection and treatment lead to a better prognosis.
Language	English
Publishing date	2022-04-22
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.24386
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Article ; Online: Ex vivo gene modification therapy for genetic skin diseases-recent advances in gene modification technologies and delivery.

Jayarajan, Vignesh / Kounatidou, Evangelia / Qasim, Waseem / Di, Wei-Li

Experimental dermatology

2021 Volume 30, Issue 7, Page(s) 887–896

Abstract: Genetic skin diseases, also known as genodermatoses, are inherited disorders affecting skin and constitute a large and heterogeneous group of diseases. While genodermatoses are rare with the prevalence rate of less than 1 in 50,000 - 200,000, they ... ...

Abstract	Genetic skin diseases, also known as genodermatoses, are inherited disorders affecting skin and constitute a large and heterogeneous group of diseases. While genodermatoses are rare with the prevalence rate of less than 1 in 50,000 - 200,000, they frequently occur at birth or early in life and are generally chronic, severe, and could be life-threatening. The quality of life of patients and their families are severely compromised by the negative psychosocial impact of disease, physical manifestations, and the lack or loss of autonomy. Currently, there are no curative treatments for these conditions. Ex vivo gene modification therapy that involves modification or correction of mutant genes in patients' cells in vitro and then transplanted back to patients to restore functional gene expression has being developed for genodermatoses. In this review, the ex vivo gene modification therapy strategies for genodermatoses are reviewed, focusing on current advances in gene modification and correction in patients' cells and delivery of genetically modified cells to patients with discussions on gene therapy trials which have been performed in this area.
MeSH term(s)	Gene Editing ; Genetic Therapy ; Humans ; Keratinocytes ; Skin Diseases, Genetic/therapy
Language	English
Publishing date	2021-03-11
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1130936-2
ISSN	1600-0625 ; 0906-6705
ISSN (online)	1600-0625
ISSN	0906-6705
DOI	10.1111/exd.14314
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