Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities DOI Creative Commons
Nanhao Yin, Xintong Li, Xuanwei Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 22, 2024

Abstract Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance toxicity still remain. Due the advancement of immuno-oncology, an increasing number novel immunoregulatory targets mechanisms are being revealed, with relevant therapies promising improve clinical immunotherapy in foreseeable future. Therefore, comprehending larger picture is important. In this review, we analyze summarize current landscape preclinical translational mechanistic research, drug development, trials that brought about next-generation pharmacological anti-cancer agents candidates beyond classical immune checkpoint inhibitors. Along further clarification immunobiology advances antibody engineering, targeting additional inhibitory checkpoints, including LAG-3, TIM-3, TIGIT, CD47, B7 family members becoming important part research discovery, as structurally functionally optimized agonists co-stimulatory molecules T cells. Exemplified bispecific cell engagers, newly emerging bi-specific multi-specific antibodies can provide considerable benefits. Next-generation also include epigenetic drugs cytokine-based therapeutics. Cell therapies, vaccines, oncolytic viruses not covered review. This comprehensive review might aid development fastest possible adoption effective immuno-oncology modalities for benefit patients.

Language: Английский

γδ T cells in tissue physiology and surveillance DOI
Julie C. Ribot, Noëlla Lopes, Bruno Silva‐Santos

et al.

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 21(4), P. 221 - 232

Published: Oct. 14, 2020

Language: Английский

Citations

359
Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells DOI Open Access
Benjamin Ruf, Bernd Heinrich, Tim F. Greten

et al.

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 18(1), P. 112 - 127

Published: Nov. 24, 2020

Language: Английский

Citations

235
Cancer immunotherapy with γδ T cells: many paths ahead of us DOI Creative Commons
Dieter Kabelitz,

Ruben Serrano,

Léonce Kouakanou

et al.

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 17(9), P. 925 - 939

Published: July 22, 2020

γδ T cells play uniquely important roles in stress surveillance and immunity for infections carcinogenesis. Human recognize kill transformed independently of human leukocyte antigen (HLA) restriction, which is an essential feature conventional αβ cells. Vγ9Vδ2 cells, prevail the peripheral blood healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates a mechanism dependent on butyrophilin molecules. expressing other cell receptor variable genes, notably Vδ1, more abundant mucosal tissue. In addition to receptor, usually express activating natural killer (NK) receptors, such as NKp30, NKp44, NKG2D binds stress-inducible surface molecules that absent but frequently expressed malignant Therefore, endowed with at least two independent recognition systems sense tumor initiate anticancer effector mechanisms, including cytokine production cytotoxicity. view their HLA-independent potent antitumor activity, there has been increasing interest translating unique potential into innovative cellular cancer immunotherapies. Here, we discuss recent developments enhance efficacy cell-based immunotherapy. This includes strategies vivo activation tumor-targeting optimization vitro expansion protocols, development gene-modified It equally consider synergisms therapeutic strategies, checkpoint inhibitors, chemotherapy, (local) innate immunity.

Language: Английский

Citations

229
The emerging roles of γδ T cells in cancer immunotherapy DOI
Sofia Mensurado, Rafael Blanco-Domínguez, Bruno Silva‐Santos

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(3), P. 178 - 191

Published: Jan. 9, 2023

Language: Английский

Citations

198
Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer DOI Creative Commons
Yan Xu, Zheng Xiang, Mohammed Alnaggar

et al.

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 18(2), P. 427 - 439

Published: Sept. 16, 2020

Abstract Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy. Due to their HLA-independent mode of action, allogeneic can be considered clinical application. To apply in adoptive immunotherapy, the methodology used obtain adequate cell numbers with optimal effector function vitro needs optimized, and safety efficacy also need proven. Therefore, we developed a novel formula improve expansion peripheral γδ from healthy donors. Then, humanized mouse model validate therapeutic expanded vivo; furthermore, were adoptively transferred into late-stage liver lung cancer patients. We found that possessed significantly improved immune functions, including proliferation, differentiation, killing, both model. Furthermore, phase I trial 132 patients total 414 infusions unequivocally validated cells. Among these patients, 8 10 who received ≥5 showed greatly prolonged survival, which preliminarily verified T-cell therapy. Our studies underscore will inspire further investigations eventually benefit

Language: Английский

Citations

181
The landscape of bispecific T cell engager in cancer treatment DOI Creative Commons
Yingtang Zhou, Ming‐Guo Liu, Fei Ren

et al.

Biomarker Research, Journal Year: 2021, Volume and Issue: 9(1)

Published: May 26, 2021

T cell-based immunotherapies have revolutionized treatment paradigms in various cancers, however, limited response rates secondary to lack of significant T-cell infiltration the tumor site remain a major problem. To address this limitation, strategies for redirecting cells treat cancer are being intensively investigated, while bispecific cell engager (BiTE) therapy constitutes one most promising therapeutic approaches. BiTE is antibody construct with unique function, simultaneously binding an antigen on and surface molecule induce lysis. represented by blinatumomab has achieved impressive efficacy B malignancies. However, mechanisms resistance associated loss immunosuppressive factors such as upregulation immune checkpoints. Thus, modification constructs searching combination designed further enhance well reduce toxicity become urgent issue, especially solid tumors which always poor. In particular, focusing innate immunity attracted increasing interest shown anti-tumor activity engaging or innate-like cells, can be used alone complement current therapies. review, we depict landscape therapy, including clinical advances potential predictors, challenges resistance, developments novel therapy.

Language: Английский

Citations

156
Natural killer cell homing and trafficking in tissues and tumors: from biology to application DOI Creative Commons
Guanghe Ran,

Yu qing Lin,

Lei Tian

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 29, 2022

Abstract Natural killer (NK) cells, a subgroup of innate lymphoid act as the first line defense against cancer. Although some evidence shows that NK cells can develop in secondary tissues, mainly bone marrow (BM) and egress into blood circulation when they mature. They then migrate to settle down peripheral though special subsets home back BM or organs. Owing its success allogeneic adoptive transfer for cancer treatment “off-the-shelf” potential, cell-based immunotherapy is attracting increasing attention various cancers. However, insufficient infiltration adoptively transferred limits clinical utility, especially solid tumors. Expansion engineered chimeric antigen receptor (CAR) ex vivo prior by using cytokines alters profiles chemokine receptors, which affects tumor tissue. Several factors control cell trafficking homing, including cell-intrinsic (e.g., transcriptional factors), cell-extrinsic integrins, selectins, chemokines their corresponding signals induced cytokines, sphingosine-1-phosphate (S1P), etc.), cellular microenvironment. Here, we summarize mechanisms homing at steady state during development, aiming improve immunotherapy.

Language: Английский

Citations

152
Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments DOI
Noëlla Lopes, Claire L. McIntyre,

Stefania Martin

et al.

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(2), P. 179 - 192

Published: Jan. 18, 2021

Language: Английский

Citations

150
Advances in Universal CAR-T Cell Therapy DOI Creative Commons
Haolong Lin, Jiali Cheng, Wei Mu

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 6, 2021

Chimeric antigen receptor T (CAR-T) cell therapy achieved extraordinary achievements results in antitumor treatments, especially against hematological malignancies, where it leads to remarkable, long-term antineoplastic effects with higher target specificity. Nevertheless, some limitations persist autologous CAR-T therapy, such as high costs, long manufacturing periods, and restricted sources. The development of a universal (UCAR-T) is an attractive breakthrough point that may overcome most these drawbacks. Here, we review the progress challenges focusing on comprehensive comparison UCAR-T original therapy. Furthermore, summarize developments concerns about safety efficiency Finally, address other immune cells, which might be promising candidates complement for cells. Through detailed overview, describe current landscape explore prospect

Language: Английский

Citations

140
Function of γδ T cells in tumor immunology and their application to cancer therapy DOI Creative Commons
Jang Hyun Park, Heung Kyu Lee

Experimental & Molecular Medicine, Journal Year: 2021, Volume and Issue: 53(3), P. 318 - 327

Published: March 1, 2021

Abstract T cells of the γδ lineage are unconventional with functions not restricted to MHC-mediated antigen presentation. Because their broad specificity and NK-like cytotoxicity, T-cell importance in tumor immunology has been emphasized. However, some subsets, especially those expressing IL-17, immunosuppressive or tumor-promoting cells. Their cytokine profile cytotoxicity seemingly determined by cross-talk microenvironment components, γδTCR chain. Furthermore, much about TCR remains unknown compared extreme diversity chain pairs. Thus, investigation application have relatively difficult. Nevertheless, remain attractive targets for antitumor therapy because independence from MHC molecules. ability evade immune system through shedding, heterogeneous antigens, low spreading, MHC-independent represent good alternative immunotherapy. Therefore, many approaches using attempted, including induction endogenous cell activation, adoptive transfer expanded ex vivo, utilization chimeric receptor (CAR)-T Here, we discuss function cancer therapy.

Language: Английский

Citations

137