Managing hypogammaglobulinemia in patients treated with CAR-T-cell therapy: key points for clinicians DOI
Eleftheria Kampouri, Carla S. Walti, Jordan Gauthier

et al.

Expert Review of Hematology, Journal Year: 2022, Volume and Issue: 15(4), P. 305 - 320

Published: April 3, 2022

Introduction The unprecedented success of chimeric antigen receptor (CAR)-T-cell therapy in the management B-cell malignancies comes with a price specific side effects. Healthy depletion is an anticipated ‘on-target’ ‘off-tumor’ effect and can contribute to severe prolonged hypogammaglobulinemia. Evidence-based guidelines for use immunoglobulin replacement (IGRT) infection prevention are lacking this population.Areas Covered This article reviews mechanisms epidemiology hypogammaglobulinemia antibody deficiency, association infections, strategies address these issues CD19- BCMA-CAR-T-cell recipients.Expert Opinion CD19 BCMA CAR-T-cell result unique immune deficits due B-lineage cells may require different strategies. Hypogammaglobulinemia before after frequent, but data on efficacy cost-effectiveness IGRT lacking. Monthly should be prioritized patients or recurrent bacterial infections. more broadly necessary prevent infections recipients children irrespective history. Vaccinations indicated augment humoral immunity immunogenic despite cytopenias; re-vaccination(s) required. Controlled trials needed better understand role vaccines population.

Language: Английский

Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity DOI Creative Commons
Marco Romano, Giorgia Fanelli,

Caraugh Jane Albany

et al.

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Jan. 31, 2019

Regulatory T cells (Tregs) are important for the induction and maintenance of peripheral tolerance therefore, they key in preventing excessive immune responses autoimmunity. In last decades, several reports have been focussed on understanding biology Tregs their mechanisms action. Preclinical studies demonstrated ability to delay/prevent graft rejection control autoimmune following adoptive transfer vivo. Due these promising results, extensively studied as a potential new tool prevention and/or treatment diseases. Currently, solid organ transplantation remains choice end-stage failure. However, chronic ensuing side effects immunosuppressants represent main limiting factors acceptance patient survival. Autoimmune disorders diseases caused by breakdown against self-antigens. This is triggered either numerical or functional Treg defect, resistance effector suppression. this scenario, patients receiving high doses immunosuppressant left susceptible life-threatening opportunistic infections increased risk malignancies. 10 years, few phase I clinical trials aiming investigate safety feasibility Treg-based therapy completed published, whilst an increasing numbers still ongoing. The first results showed II already enrolling. review, we describe our focussing primarily ontogenesis, action methods used clinic isolation expansion. Furthermore, will ongoing from with setting disorders. Finally, discuss strategies further improve success therapy.

Language: Английский

Citations

454
The Emerging Landscape of Immune Cell Therapies DOI Creative Commons
Evan W. Weber, Marcela V. Maus, Crystal L. Mackall

et al.

Cell, Journal Year: 2020, Volume and Issue: 181(1), P. 46 - 62

Published: April 1, 2020

Language: Английский

Citations

363
CAR T therapy beyond cancer: the evolution of a living drug DOI
Daniel Baker, Zoltàn Arany, Joseph A. Baur

et al.

Nature, Journal Year: 2023, Volume and Issue: 619(7971), P. 707 - 715

Published: July 26, 2023

Language: Английский

Citations

242
Engineered cellular immunotherapies in cancer and beyond DOI
Amanda Finck,

Tatiana Blanchard,

Christopher P. Roselle

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(4), P. 678 - 689

Published: April 1, 2022

Language: Английский

Citations

209
Control of human toxoplasmosis DOI Creative Commons
Nicholas C. Smith, Cibelly Goulart, Jenni A. Hayward

et al.

International Journal for Parasitology, Journal Year: 2020, Volume and Issue: 51(2-3), P. 95 - 121

Published: Dec. 19, 2020

Toxoplasmosis is caused by Toxoplasma gondii, an apicomplexan parasite that able to infect any nucleated cell in warm-blooded animal. gondii infects around 2 billion people and, whilst only a small percentage of infected will suffer serious disease, the prevalence makes it one most damaging zoonotic diseases world. disease with multiple manifestations: can cause fatal encephalitis immunosuppressed people; if first contracted during pregnancy, miscarriage or congenital defects neonate; and ocular even immunocompetent people. The has complex epidemiology, being transmitted ingestion oocysts are shed faeces definitive feline hosts contaminate water, soil crops, consumption intracellular cysts undercooked meat from intermediate hosts. In this review we examine current future approaches control toxoplasmosis, which encompass variety measures target different components life cycle T. gondii. These include: education programs about avoidance contact infectious stages; biosecurity sanitation ensure food water safety; chemo- immunotherapeutics active infections disease; prophylactic options prevent acquisition infection livestock cyst formation meat; vaccines shedding

Language: Английский

Citations

207
Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany DOI Creative Commons
Nawid Albinger, Jessica Hartmann, Evelyn Ullrich

et al.

Gene Therapy, Journal Year: 2021, Volume and Issue: 28(9), P. 513 - 527

Published: March 22, 2021

Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. Lately, CAR-NK have also come into focus as novel therapeutic options to address hurdles related CAR-T therapies, such therapy-induced side effects. Currently, more than 500 and 17 trials being conducted worldwide including four products Kymriah, Yescarta, Tecartus Breyanzi, which already available market. Most cell-based gene therapy that under clinical evaluation consist autologous enriched T cells, whereas approaches can be generated from allogeneic donors. Besides modification based a second-generation CAR, advanced CAR-immune therapeutics tested, utilize precise insertion genes circumvent graft-versus-host disease (GvHD) or employ dual targeting approach adapter CARs in order avoid resistance caused by loss. In this review, we going take closer look at commercial well products, currently trials, Germany.

Language: Английский

Citations

196
Treg Enhancing Therapies to Treat Autoimmune Diseases DOI Open Access
Peter J. Eggenhuizen, Boaz H. Ng, Joshua D. Ooi

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(19), P. 7015 - 7015

Published: Sept. 23, 2020

Regulatory T cells (Tregs) are a small yet critical subset of CD4+ cells, which have the role maintaining immune homeostasis by, for example, regulating self-tolerance, tumor immunity, anti-microbial resistance, allergy and transplantation rejection. The suppressive mechanisms by Tregs function varied pleiotropic. ability to maintain self-tolerance means they control prevention autoimmune diseases. Irregularities in Treg number can result loss tolerance disease. Restoring through promotion, activation or delivery has emerged as focus therapies aimed at curing controlling Such focused on cell using drugs suppress effector promote Tregs. Other approaches trialed inducing administering autoantigen via direct administration, transient expression DNA vector, antigen-specific nanoparticles. More recently, cell-based been developed an approach directly indirectly enhance specificity, number. This be achieved transfer tolerogenic dendritic potential expand cells. administered treat disease way polyclonal transduced with receptor high affinity target autoantigen, such (TCR) chimeric antigen (CAR). review will discuss strategies being redirect responses state tolerance, aim amelioration

Language: Английский

Citations

194
Cell Therapy: Types, Regulation, and Clinical Benefits DOI Creative Commons
Abed El-Hakim El-Kadiry, Moutih Rafei,

Riam Shammaa

et al.

Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 8

Published: Nov. 22, 2021

Cell therapy practices date back to the 19 th century and continue expand on investigational investment grounds. includes stem cell- non–stem cell-based, unicellular multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, regulatory levels. Following steps their predecessor cell therapies that have become established or commercialized, premarket approval-exempt provide patients promising therapeutic benefits in disease areas. In this review article, we delineate vast types therapy, including cell-based create first-in-literature compilation “multicellular” used clinical settings. Besides providing nuts bolts FDA policies regulating use, discuss reported 3 areas—regenerative medicine, immune diseases, cancer. Finally, contemplate recent attention shift toward combined approaches, highlighting factors render a more attractive option than counterparts.

Language: Английский

Citations

161
Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies DOI Creative Commons

Xinyi Xiao,

Shengkang Huang,

Sifei Chen

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: Nov. 18, 2021

Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR products have been approved by the US Food Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to development of therapy, most notably cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity (ICANS). Understanding mechanisms underlying these establishing prevention strategies are important. In this review, we summarize CRS ICANS provide potential strategies.

Language: Английский

Citations

158
Human immunology and immunotherapy: main achievements and challenges DOI Open Access

Jezabel Varadé,

Susana Magadán, África González‐Fernández

et al.

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 18(4), P. 805 - 828

Published: Sept. 2, 2020

Language: Английский

Citations

156