A novel human anti-TIGIT monoclonal antibody with excellent function in eliciting NK cell-mediated antitumor immunity

Han, Dongyi; Xu, Yinfeng; Zhao, Xinping; Mao, Yunyun; Kang, Qinglin; Wen, Weihong; Yu, Xiaoyan; Xu, Li; Liu, Fujia; Zhang, Mengyao; Cui, Jiazhen; Wang, Zhang; Yang, Zhen; Du, Peng; Qin, Weijun

doi:10.1016/j.bbrc.2020.12.013

Cited by 14 publications

(8 citation statements)

References 15 publications

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“…As one of the most commonly targeted immune checkpoint 67 and the core of a complex regulatory network included CD96, CD112R, CD226, CD155 and CD226 7 , TIGIT has been considered as a potential ICBs to develop novel immunotherapy strategies. Several preclinical studies have shown that TIGIT blockade alone could impede the growth and proliferation of the tumors 68 – 70 , even in anti-PD-1 resistant tumor model 8 . Moreover, combining the TIGIT blockade with PD-1 blockade 71 , 72 , IL-15 stimulation 73 or optimized fractionated radiotherapy 74 , could promote the response to immunotherapy and increase the survival in animal models.…”

Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis revealing the role of TIGIT in tumor microenvironment

Wen

Mao

Cheng

et al. 2021

Sci Rep

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T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), an immune checkpoint, plays a pivotal role in immune suppression. However its role in tumor immunity and correlation with the genetic and epigenetic alterations remains unknown. Here, we comprehensively analyzed the expression patterns of the TIGIT and its value of prognostic prediction among 33 types of cancers based on the data collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression projects (GTEx). Furthermore, the correlations of TIGIT with pathological stages, tumor-infiltrating immune cells (TIICs), signatures of T cells subtypes, immune checkpoint genes, the degree of Estimation of STromal and Immune cells in MAlignant Tumor tissues using the Expression data (ESTIMATE), tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) genes, and DNA methyltransferases (DNMTs) were also explored. Gene functional enrichment was conducted by Gene Set Enrichment Analysis (GSEA). Our results showed that the expression of TIGIT was upregulated in most of the cancer types. Cox regression model showed that high expression of TIGIT in tumor samples correlates with poor prognosis in KIRC, KIRP, LGG, UVM, and with favorable prognosis in BRCA, CECS, HNSC, SKCM. TIGIT expression positively correlated with advanced stages, TIICs, the signatures of effector T cells, exhausted T cells, effector Tregs and the degree of ESTIMATE in KIRC, KIRP and UVM. TIGIT expression also positively correlated with CTLA4, PDCD1 (PD-1), CD274 (PD-L1), ICOS in most of the cancer types. Furthermore, the expression of TIGIT was correlated with TMB, MSI, MMR genes and DNMTs in different types of cancers. GSEA analysis showed that the expression of TIGIT was related to cytokine-cytokine receptor interaction, allograft rejection, oxidative phosphorylation. These findings suggested that TIGIT could serve as a potential biomarker for prognosis and a novel target for immunotherapies in cancers.

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Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis revealing the role of TIGIT in tumor microenvironment

Wen

Mao

Cheng

et al. 2021

Sci Rep

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“…TIGIT is a novel checkpoint target, and antibodies targeting this checkpoint have proven effective. A novel anti-TIGIT mAb, AET2010, holds promise for preventing NK cell exhaustion and inducing anti-tumor NK cell immunity, both ex vivo and in vivo [ 98 ].…”

Section: Nk Cell Therapies For Nsclcmentioning

confidence: 99%

Harnessing Natural Killer Cells in Non-Small Cell Lung Cancer

Russell

Conroy

Barr

2022

Cells

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Lung cancer is the leading cause of cancer-related deaths worldwide. There are two main subtypes: small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). NSCLC accounts for 85% of lung cancer diagnoses. Early lung cancer very often has no specific symptoms, and many patients present with late stage disease. Despite the various treatments currently available, many patients experience tumor relapse or develop therapeutic resistance, highlighting the need for more effective therapies. The development of immunotherapies has revolutionized the cancer treatment landscape by enhancing the body’s own immune system to fight cancer. Natural killer (NK) cells are crucial anti-tumor immune cells, and their exclusion from the tumor microenvironment is associated with poorer survival. It is well established that NK cell frequencies and functions are impaired in NSCLC; thus, placing NK cell-based immunotherapies as a desirable therapeutic concept for this malignancy. Immunotherapies such as checkpoint inhibitors are transforming outcomes for NSCLC. This review explores the current treatment landscape for NSCLC, the role of NK cells and their dysfunction in the cancer setting, the advancement of NK cell therapies, and their future utility in NSCLC.

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“…Furthermore, blockade of TIGIT resulted in potent tumor-specific T-cell immunity in an NK cell-dependent manner, enhanced therapeutic effects with PD-1-targeted therapy and sustained memory immunity in tumour rechallenge models 26. Novel anti-TIGIT monoclonal antibodies with the specific purpose of enhancing NK-cell immunity such as AET2010 are currently being developed and tested in in vivo settings 47…”

Section: Tigit Expression In Malignancymentioning

confidence: 99%

Gene of the month: T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)

et al. 2022

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Immune modulators play a crucial role in carcinogenesis and cancer progression by impairing cancer cell-targeted immune responses. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) regulates T-cell function and cancer cell recognition and was therefore identified as a promising target for cancer immunotherapy. TIGIT is expressed in T cells and natural killer (NK) cells and has three ligands: CD155, CD112 and CD113. CD155 binds TIGIT with the highest affinity and promotes direct and indirect downregulation of T-cell response. TIGIT signalling further inhibits NK function and secretion of proinflammatory cytokines. An association between TIGIT expression and poor survival was identified in multiple cancer entities. Blocking TIGIT with monoclonal antibodies, and a combination of TIGIT and programmed cell death protein 1 blockade in particular, prevented tumour progression, distant metastasis and tumour recurrence in in vivo models. Inhibition of TIGIT is currently evaluated in first clinical trials.

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A novel human anti-TIGIT monoclonal antibody with excellent function in eliciting NK cell-mediated antitumor immunity

Cited by 14 publications

References 15 publications

A pan-cancer analysis revealing the role of TIGIT in tumor microenvironment

A pan-cancer analysis revealing the role of TIGIT in tumor microenvironment

Harnessing Natural Killer Cells in Non-Small Cell Lung Cancer

Gene of the month: T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)

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