Optimising CAR T therapy for the treatment of solid tumors DOI Creative Commons

Norhan Mobark,

Caroline Hull,

John Maher

et al.

Expert Review of Anticancer Therapy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 17

Published: Oct. 28, 2024

Introduction Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely to be resistant this therapeutic modality. Challenges include paucity safe target antigens, heterogeneity expression within tumor, difficulty delivery CAR site disease, poor penetration tumor deposits inability circumvent array immunosuppressive biophysical barriers imposed by microenvironment.

Language: Английский

Alloreactive-free CAR-VST therapy: a step forward in long-term tumor control in viral context DOI Creative Commons
Valentine Wang, Barbara Savoldo, J. Guimarães

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

CAR-T cell therapy has revolutionized immunotherapy but its allogeneic application, using various strategies, faces significant challenges including graft-versus-host disease and graft rejection. Recent advances Virus Specific T cells to generate CAR-VST have demonstrated potential for enhanced persistence antitumor efficacy, positioning CAR-VSTs as a promising alternative conventional in an setting. This review provides comprehensive overview of development, emphasizing strategies mitigate immunogenicity, such specialized TCR, approaches improve therapeutic against host immune responses. In this review, we discuss the production methods explore optimization enhance their functionality, activation profiles, memory persistence, exhaustion resistance. Emphasis is placed on unique dual specificity both antiviral responses, along with in-depth examination preclinical clinical outcomes. We highlight how these contribute efficacy durability settings, offering new perspectives broad applications. By focusing key mechanisms that enable address autologous challenges, highlights strategy developing effective therapies.

Language: Английский

Citations

0
Clinical evidence of immunogenicity of CAR-T cell therapies and its implication in the clinical development of CAR-T drug products DOI Creative Commons
Hammodah R. Alfar,

Cecil Chen,

Eric J. Lachacz

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 21, 2025

Chimeric antigen receptor-engineered T cell therapies (CAR-T) are becoming powerful immunotherapeutic tools for treating malignancies, especially hematological malignancies. Like other biological drugs, CAR-T products can trigger unwanted immune responses in patients receiving the treatment. This might lead to treatment failure or life-threatening consequences. immunogenicity could also affect cells' cellular kinetics and clinical responses. In this review, we summarize of biologics their effects on PK/PD profiles, safety, efficacy. We introduce mechanisms induced by cells evidence currently FDA-approved products. Particularly, available data from each product's trials, assays, sample types, preclinical efficacy models, which were retrieved FDA EMA websites. discuss a model that is promising evaluating immunogenicity.

Language: Английский

Citations

0
CAR‐T Cell Manufacturing for Hematological and Solid Tumors: From the Preclinical to Clinical Point of View DOI Creative Commons
Sara Capolla, Maria Rasool, Giuseppe Toffoli

et al.

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(5)

Published: Feb. 27, 2025

ABSTRACT Cell therapy based on chimeric antigen receptor (CAR) T cells has represented a revolutionary new approach for treating tumors, especially hematological diseases. Complete remission rates (CRR) > 80%–97% and 50%–90% overall response (ORR) have been achieved with treatment CAR‐T in patients malignant B‐cell tumors that relapsed or are refractory to previous treatments. Toxicity remains the major problem. Most treated develop high‐grade cytokine release syndrome (CRS) immune effector cell‐associated neurotoxicity (ICANS). However, unprecedentedly high CRR ORR led approval of six cell therapeutics by Food Drug Administration (FDA) European Medicines Agency (EMA), prompting researchers improve existing products ones. By now, around 1000 clinical trials registered at ClinicalTrials.gov : 82% diseases, while remaining 16% solid tumors. As result this increased research, an enormous amount conflicting information accumulated literature, each group follows its manufacturing protocols performs specific vitro testing. This review aimed combine compare preclinical information, highlighting most used provide comprehensive overview world cells, from their characterization. The focus is all steps process, collection patient donor blood enrichment activation anti‐CD3/CD28 beads, interleukin‐2 (IL‐2) IL‐7 IL‐15 (induction more functional memory phenotype), transfection (viral non‐viral methods). Automation crucial ensuring standardized final product.

Language: Английский

Citations

0
Exploration of the role of immune cells and cell therapy in hepatocellular carcinoma DOI Creative Commons
Tao Zhang, Chongyang Ren, Zhanyu Yang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Hepatocellular carcinoma stands as one of the foremost contributors to cancer-associated fatalities globally, and limitations traditional treatment methods have prompted researchers explore new therapeutic options. Recently, cell therapy has emerged a promising approach for HCC, showing significant potential in improving patient outcomes. This review article explores use covering different types, mechanisms behind their effectiveness, recent advancements clinical trials, ongoing challenges. aims provide insightful perspectives future research applications treating HCC by synthesizing current knowledge.

Language: Английский

Citations

0
CAR T-cell therapy in renal cell carcinoma: opportunities, challenges, and new strategies to overcome DOI
Mahan Mohammadi, Houshang Najafi, Pantea Mohammadi

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(6)

Published: April 24, 2025

Language: Английский

Citations

0
Optimising CAR T therapy for the treatment of solid tumors DOI Creative Commons

Norhan Mobark,

Caroline Hull,

John Maher

et al.

Expert Review of Anticancer Therapy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 17

Published: Oct. 28, 2024

Introduction Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely to be resistant this therapeutic modality. Challenges include paucity safe target antigens, heterogeneity expression within tumor, difficulty delivery CAR site disease, poor penetration tumor deposits inability circumvent array immunosuppressive biophysical barriers imposed by microenvironment.

Language: Английский

Citations

0