B7-H3 Overexpression Predicts Poor Survival of Cancer Patients: A Meta-Analysis

Ye, Zhimeng; Zheng, Zhuojun; Li, Xiaodong; Zhu, Yuandong; Zhong, Zhao-ping; Peng, Lan; Wu, Yanyan

doi:10.1159/000447859

Cited by 48 publications

(33 citation statements)

References 58 publications

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“…There is a limited expression of B7-H3 on various normal tissues such as pancreas, liver, small intestine, colon, heart, thymus, spleen, placenta, and testis (357). However, aberrant expression of B7-H3 is seen in various malignancies in which it is associated with poor outcome, including RCC, breast cancer, lung cancer, esophageal squamous cancer, gastric cancer, pancreatic cancer, gallbladder cancer, colorectal cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, osteosarcoma, and neuroblastoma (358,359). Circulating serum B7-H3 levels are significantly higher in patients with lung cancer, renal cell carcinoma, hepatocellular carcinoma, colorectal carcinoma, and glioma than in healthy volunteers (360).…”

Section: B7-h3mentioning

confidence: 99%

NK Cell-Based Immune Checkpoint Inhibition

Arooj²,

2020

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Immunotherapy, with an increasing number of therapeutic dimensions, is becoming an important mode of treatment for cancer patients. The inhibition of immune checkpoints, which are the source of immune escape for various cancers, is one such immunotherapeutic dimension. It has mainly been aimed at T cells in the past, but NK cells are a newly emerging target. Simultaneously, the number of checkpoints identified has been increasing in recent times. In addition to the classical NK cell receptors KIRs, LIRs, and NKG2A, several other immune checkpoints have also been shown to cause dysfunction of NK cells in various cancers and chronic infections. These checkpoints include the revolutionized CTLA-4, PD-1, and recently identified B7-H3, as well as LAG-3, TIGIT & CD96, TIM-3, and the most recently acknowledged checkpoint-members of the Siglecs family (Siglec-7/9), CD200 and CD47. An interesting dimension of immune checkpoints is their candidacy for dual-checkpoint inhibition, resulting in therapeutic synergism. Furthermore, the combination of immune checkpoint inhibition with other NK cell cytotoxicity restoration strategies could also strengthen its efficacy as an antitumor therapy. Here, we have undertaken a comprehensive review of the literature to date regarding NK cell-based immune checkpoints.

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Section: B7-h3mentioning

confidence: 99%

NK Cell-Based Immune Checkpoint Inhibition

Arooj²,

2020

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“…25 Several studies have also shown that B7-H3 overexpression is associated with tumor progression, metastatic potential and a poor prognosis. [26][27][28][29] The immunemodulatory functions of B7-H3 remain controversial, with data supporting both stimulatory and inhibitory roles in T cell immunity in different model systems. 30 A monoclonal antibody (mAb) recognizing B7-H3 is being used to treat refractory pediatric brain cancers and thus far the clinical trial has yielded safe and promising results.…”

Section: Introductionmentioning

confidence: 99%

B7-H3 specific T cells with chimeric antigen receptor and decoy PD-1 receptors eradicate established solid human tumors in mouse models

et al. 2019

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The application of chimeric antigen receptor (CAR)-T cell therapy in patients with advanced solid tumors remains a significant challenge. Simultaneously targeting antigen and the solid tumor microenvironment are two major factors that greatly impact CART cell therapy outcomes. In this study, we engineered CART cells to specifically target B7-H3, a protein commonly found in solid human tumors, using a single-chain variable fragment (scFv) derived from an anti-B7-H3 monoclonal antibody. We tested the antitumor activity of B7-H3 CART cells in mouse models with solid human tumors and determined that B7-H3 CART cells exhibited potent antitumor activity against B7-H3 + tumor cells in vitro and in vivo. In addition, PD-1 decoy receptors were engineered to include extracellular PD-1 fused to the intracellular stimulatory domain of either CD28 or IL-7 receptor, respectively, which were then introduced into B7-H3 CART cells. As a result, these newly modified, superior CART cells exhibited more persistent antitumor activity in B7-H3 + /B7-H1 + tumors in vivo. Our findings indicate that B7-H3 specific CART cells have the potential to treat multiple types of advanced solid tumors.

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“…B7-H3 (CD276) is a checkpoint molecule expressed at high levels on many pediatric solid tumors including neuroblastoma ( 128 – 131 ). It plays a role in immune evasion ( 132 ) and metastatic potential ( 133 ), and overexpression correlates with poor prognosis in many cancers ( 134 ). These characteristics have made B7-H3 an attractive target for immunotherapeutic strategies, and early phase clinical trials with monoclonal antibodies have demonstrated encouraging results in both neuroblastoma and other malignancies ( 135 – 137 ).…”

Section: Challenges In Targeting Neuroblastoma With Car T Cellsmentioning

confidence: 99%

CAR T Cell Therapy for Neuroblastoma

2018

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Patients with high risk neuroblastoma have a poor prognosis and survivors are often left with debilitating long term sequelae from treatment. Even after integration of anti-GD2 monoclonal antibody therapy into standard, upftont protocols, 5-year overall survival rates are only about 50%. The success of anti-GD2 therapy has proven that immunotherapy can be effective in neuroblastoma. Adoptive transfer of chimeric antigen receptor (CAR) T cells has the potential to build on this success. In early phase clinical trials, CAR T cell therapy for neuroblastoma has proven safe and feasible, but significant barriers to efficacy remain. These include lack of T cell persistence and potency, difficulty in target identification, and an immunosuppressive tumor microenvironment. With recent advances in CAR T cell engineering, many of these issues are being addressed in the laboratory. In this review, we summarize the clinical trials that have been completed or are underway for CAR T cell therapy in neuroblastoma, discuss the conclusions and open questions derived from these trials, and consider potential strategies to improve CAR T cell therapy for patients with neuroblastoma.

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B7-H3 Overexpression Predicts Poor Survival of Cancer Patients: A Meta-Analysis

Cited by 48 publications

References 58 publications

NK Cell-Based Immune Checkpoint Inhibition

NK Cell-Based Immune Checkpoint Inhibition

B7-H3 specific T cells with chimeric antigen receptor and decoy PD-1 receptors eradicate established solid human tumors in mouse models

CAR T Cell Therapy for Neuroblastoma

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