Allogeneic CD19 CAR T cells armed with an anti-rejection CD70 CAR overcome antigen escape and evade alloimmune responses DOI Creative Commons
Elvin J. Lauron, Kristen Zhang, Zhe Li

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 20, 2025

Abstract Allogeneic chimeric antigen receptor (CAR) T cells can achieve sustained clinical benefit in B cell malignancies and autoimmune diseases. Despite the many potential advantages over autologous products, allogeneic CAR carry a higher risk of rejection, which may limit persistence therapeutic efficacy. We report design evaluation an optimized CD70 that prevents rejection by targeting activated alloreactive lymphocytes. Co-expression this with CD19 resulted presence lymphocytes prolonged antitumor activity escape model. In vivo, CD19/CD70 dual resisted eliminated CD70+ from patients systemic lupus erythematosus, lowering immunoglobulin production. An therapy therefore reduce need for lymphodepleting conditioning regimens required prior to infusion.

Язык: Английский

Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors DOI Creative Commons
Salma Khan, Yeonjoo Choi, Mysore S. Veena

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 6, 2025

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, extension these successes to solid tumors remains limited due several intrinsic challenges, including heterogeneity immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview recent advances in CAR aimed at overcoming obstacles. We discuss importance identification by emphasizing tumor-specific tumor-associated antigens development antigens. Furthermore, highlight key structural innovations, cytokine-armored CARs, protease-regulated CARs engineered chemokine receptors, enhance infiltration activity within microenvironment. Additionally, novel manufacturing approaches, such as Sleeping Beauty transposon system, mRNA-based transfection, vivo production, are discussed scalable solution improve accessibility therapies. Finally, address critical therapeutic limitations, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), suboptimal persistence cells. An examination emerging strategies for countering limitations reveals that CRISPR-Cas9-mediated genetic modifications combination utilizing checkpoint inhibitors can functionality durability. By integrating insights from preclinical models, trials, innovative engineering review addresses their performance tumors.

Язык: Английский

Процитировано

3
Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies DOI Creative Commons
Yan-Ruide Li,

Ying Fang,

Shaoqiang Niu

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 1, 2025

Abstract Chimeric antigen receptor (CAR)-engineered T cell therapy holds promise for treating myeloid malignancies, but challenges remain in bone marrow (BM) infiltration and targeting BM-resident malignant cells. Current autologous CAR-T therapies also face manufacturing patient selection issues, underscoring the need off-the-shelf products. In this study, we characterize primary samples identify a unique therapeutic opportunity CAR-engineered invariant natural killer (CAR-NKT) Using stem gene engineering clinically guided culture method, generate allogeneic CD33-directed CAR-NKT cells with high yield, purity, robustness. preclinical mouse models, exhibit strong BM homing effectively target blast cells, including CD33-low/negative leukemia progenitor Furthermore, synergize hypomethylating agents, enhancing tumor-killing efficacy. These show minimal off-tumor toxicity, reduced graft-versus-host disease cytokine release syndrome risks, resistance to allorejection, highlighting their substantial potential malignancies.

Язык: Английский

Процитировано

3
Off-the-shelf CAR-T cells could prove paradigm shifting for autoimmune diseases DOI
Daniel Baker, Carl H. June

Cell, Год журнала: 2024, Номер 187(18), С. 4826 - 4828

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

8
Exploring CAR-macrophages in non-tumor diseases: Therapeutic potential beyond cancer DOI Creative Commons

Yizhao Chen,

Qianling Xin,

Mengjuan Zhu

и другие.

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, first approved CAR product, has demonstrated therapeutic potential treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach immune particularly solid highlighting feasibility using macrophages to eliminate pathogens abnormal cells.

Язык: Английский

Процитировано

1
Opportunities and limitations of B cell depletion approaches in SLE DOI
Marit Stockfelt, Y.K. Onno Teng, Edward M Vital

и другие.

Nature Reviews Rheumatology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Язык: Английский

Процитировано

1
Exploring new horizons in CAR-based therapy for the treatment of thyroid-associated ophthalmopathy DOI Creative Commons
Xiaohua Zhu, Weijie Zhou, Tuo Li

и другие.

Military Medical Research, Год журнала: 2025, Номер 12(1)

Опубликована: Янв. 28, 2025

Язык: Английский

Процитировано

1
Small RNA and Toll-like receptor interactions: origins and disease mechanisms DOI
Jiancheng Yu, Xu Dong Zhang, Chen Cai

и другие.

Trends in Biochemical Sciences, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
World-first therapy using donor cells sends autoimmune diseases into remission DOI

Smriti Mallapaty

Nature, Год журнала: 2024, Номер unknown

Опубликована: Окт. 4, 2024

Язык: Английский

Процитировано

4
Safety and efficacy of CAR-T cell therapy in patients with autoimmune diseases: a systematic review DOI

Lakshmi Prasanna Vaishnavi Kattamuri,

Bhavesh Mohan Lal, Nikhil Vojjala

и другие.

Rheumatology International, Год журнала: 2025, Номер 45(1)

Опубликована: Янв. 4, 2025

Язык: Английский

Процитировано

0
Highlighting individual patient data related to chimeric antigen receptor T-cell therapy in refractory autoimmune rheumatic diseases DOI Creative Commons
Mads Lamm Larsen, Anne Voss, Christoffer Tandrup Nielsen

и другие.

Scandinavian Journal of Rheumatology, Год журнала: 2025, Номер unknown, С. 1 - 6

Опубликована: Янв. 13, 2025

Язык: Английский

Процитировано

0