Trends in Cell Biology, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 1, 2024
Language: Английский
Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)
Published: Aug. 18, 2023
Abstract Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to subsequent specific enhanced T receptor (TCR)-T and chimeric antigen (CAR)-T therapies, many novel strategies cancer treatment been developed. Owing its promising outcomes, CAR-T therapy has revolutionized field ACTs, particularly hematologic malignancies. Despite these advances, still limitations in both autologous allogeneic settings, including practicality toxicity issues. To overcome challenges, researchers focused on application CAR engineering technology other types immune engineering. Consequently, several new based developed, CAR-NK, CAR-macrophage, CAR-γδT, CAR-NKT. In this review, we describe development, advantages, possible challenges aforementioned ACTs discuss current aimed at maximizing therapeutic potential ACTs. We also provide an overview various gene transduction employed immunotherapy given their importance Furthermore, possibility that capable creating a positive feedback circuit, as healthy systems do, could address flaw single type ACT, thus serve key players future immunotherapy.
Language: Английский
Citations
87
Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2388 - 2407.e9
Published: Sept. 29, 2023
Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has achieved tremendous success treating B malignancies; however, some patients fail to respond due poor autologous fitness. To improve response rates, we investigated whether disruption of the co-inhibitory receptors CTLA4 or PD-1 could restore CART function. CRISPR-Cas9-mediated deletion in preclinical models leukemia and myeloma improved CAR proliferation anti-tumor efficacy. Importantly, this effect was specific not seen upon and/or PDCD1 cells. Mechanistically, deficiency permitted unopposed CD28 signaling maintenance expression on surface under conditions high load. In clinical studies, rescued function cells from with that previously failed treatment. Thus, selective reinvigorates dysfunctional chronic lymphocytic (CLL) patient cells, providing a strategy for increasing responses therapy.
Language: Английский
Citations
79
Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 258, P. 108640 - 108640
Published: April 1, 2024
Language: Английский
Citations
21
Nature Biotechnology, Journal Year: 2024, Volume and Issue: 42(8), P. 1199 - 1217
Published: July 29, 2024
Language: Английский
Citations
19
Nature Genetics, Journal Year: 2023, Volume and Issue: 55(12), P. 2211 - 2223
Published: Nov. 9, 2023
Abstract Clinical response to adoptive T cell therapies is associated with the transcriptional and epigenetic state of product. Thus, discovery regulators gene networks their corresponding phenotypes has potential improve therapies. Here we developed pooled, CRISPR screening approaches systematically profile effects activating or repressing 120 on human CD8 + state. We found that BATF3 overexpression promoted specific features memory cells attenuated programs cytotoxicity, regulatory function, exhaustion. Upon chronic antigen stimulation, countered phenotypic signatures Moreover, enhanced potency CAR in both vitro vivo tumor models programmed a correlates positive clinical therapy. Finally, performed knockout screens defined cofactors downstream mediators network.
Language: Английский
Citations
34
Trends in cancer, Journal Year: 2024, Volume and Issue: 10(8), P. 687 - 695
Published: June 13, 2024
Chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary treatment for hematological malignancies, but its adaptation to solid tumors is impeded by multiple challenges, particularly dysfunction and exhaustion. The heterogeneity inhospitableness of the tumor microenvironment (TME) contribute diminished CAR efficacy exhibited reduced cytotoxicity, proliferation, cytokine secretion, upregulation inhibitory receptors, similar phenotype tumor-infiltrating lymphocytes (TILs). In this review, we highlight recent advances in tumors, brain cancer. Innovative strategies, including locoregional delivery 'armoring' cells with cytokines such interleukin (IL)-18, are under investigation improve safety. We also emerging issues toxicity management adverse events. This review discusses obstacles associated context outlines current future strategies overcome these challenges.
Language: Английский
Citations
17
Oncogene, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 25, 2025
Genome-wide functional genetic screening has been widely used in the biomedicine field, which makes it possible to find a needle haystack at level. In cancer research, gene mutations are closely related tumor development, metastasis, and recurrence, use of state-of-the-art powerful technologies, such as clustered regularly interspaced short palindromic repeat (CRISPR), search for most critical genes or coding products provides us with new possibility further refine mapping provide possibilities treatment patients. The CRISPR refined atlas provided Immunotherapy, highly promising method, validated clinic, but could only meet needs small proportion Finding immunotherapy targets is key future immunotherapy. Here, we revisit application immunology from different perspectives, selection diverse vitro vivo models potential immune checkpoints potentiating CAR-T cells. data will offer fresh therapeutic clues
Language: Английский
Citations
1
Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)
Published: Jan. 29, 2025
As a member of the Activator Protein-1 (AP-1) transcription factor family, Basic Leucine Zipper Transcription Factor (BATF) mediates multiple biological functions immune cells through its involvement in protein interactions and binding to DNA. Recent studies have demonstrated that BATF not only plays pivotal roles innate adaptive responses but also acts as crucial differentiation function various cells. Lines evidence indicate is associated with onset progression allergic diseases, graft-versus-host disease, tumors, autoimmune diseases. This review summarizes development cells, well immunoregulatory effects which may enhance current understanding pathogenesis diseases facilitate new therapeutic strategies.
Language: Английский
Citations
1
Nature, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 26, 2025
Language: Английский
Citations
1
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: May 15, 2025
During chronic infection and tumor progression, CD8+ T cells lose their effector functions become exhausted. These exhausted are heterogeneous comprised of progenitors that give rise to effector-like or terminally-exhausted cells. The precise cues mechanisms directing subset formation incompletely understood. Here, we show growth factor independent-1 (Gfi1) is dynamically regulated in LCMV Clone 13 infection, a previously under-described Ly108+CX3CR1+ expresses low levels Gfi1 while other established subsets have high expression. possess distinct chromatin profiles represent transitory develops cells, process dependent on Gfi1. Similarly, tumor-infiltrating required for the terminally differentiated endogenous as well anti-CTLA-induced anti-tumor responses. Taken together, key regulator
Language: Английский
Citations
1