B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

Yang, Shuo; Wei, Wei; Zhao, Qi

doi:10.7150/ijbs.41105

Cited by 177 publications

(151 citation statements)

References 53 publications

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“…Therefore, alternative targets must be considered for immunotherapy in PCa. One alternative target is the checkpoint molecule B7-H3 (CD276), whose expression has already been associated with PCa progression and worse prognosis (78) and has been suggested as a target for immunotherapy (79,80). CD276 was one of the most concordant up-regulated genes in our signature ( Figure 2) suggesting that its expression is associated with PTEN loss.…”

Section: Immunohistochemistry (Ihc) Assay Is a Clinically Utilized Tementioning

confidence: 92%

Transcriptional landscape of PTEN loss in primary prostate cancer

Imada

Sánchez

Dinalankara

et al. 2020

Preprint

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PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. Here, we applied a meta-analysis approach, leveraging two large PCa cohorts with experimentally validated PTEN and ERG status, to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. Strikingly, the signature indicates a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. With this resource, we analyzed the TCGA-PRAD cohort, creating a comprehensive transcriptomic landscape of PTEN loss in PCa that comprises both the coding and an extensive non-coding counterpart.

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Section: Immunohistochemistry (Ihc) Assay Is a Clinically Utilized Tementioning

confidence: 92%

Transcriptional landscape of PTEN loss in primary prostate cancer

Imada

Sánchez

Dinalankara

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Currently, several other B7 family ligands such as B7-H2 (a.k.a. inducible T cell costimulator ligand; ICOSL) and B7-H3 are being explored as novel immunotherapeutic targets in other cancer types (119). In HCC, both independent or combined expression of B7-H2 and B7-H3 have correlated to recurrence and poorer survival rate of the patients (120).…”

Section: Major Concerns Of Intervention(s)mentioning

confidence: 99%

Combinational Immunotherapy for Hepatocellular Carcinoma: Radiotherapy, Immune Checkpoint Blockade and Beyond

et al. 2020

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The systemic treatment landscape for advanced hepatocellular carcinoma (HCC) has experienced tremendous paradigm shift towards targeting tumor microenvironment (TME) following recent trials utilizing immune checkpoint blockade (ICB). However, limited success of ICB as monotherapy mandates the evaluation of combination strategies incorporating immunotherapy for improved clinical efficacy. Radiotherapy (RT) is an integral component in treatment of solid cancers, including HCC. Radiation mediates localized tumor killing and TME modification, thereby potentiating the action of ICB. Several preclinical and clinical studies have explored the efficacy of combining RT and ICB in HCC with promising outcomes. Greater efforts are required in discovery and understanding of novel combination strategies to maximize clinical benefit with tolerable adverse effects. This current review provides a comprehensive assessment of RT and ICB in HCC, their respective impact on TME, the rationale for their synergistic combination, as well as the current potential biomarkers available to predict clinical response. We also speculate on novel future strategies to further enhance the efficacy of this combination.

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“…B7-H3, also known as CD276, is a type I transmembrane protein that shares up to 30% amino acid identity with PD-L1 [ 10 , 11 ]. The receptor of the B7-H3 protein remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes

et al. 2021

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Background B7-H3, an immune-checkpoint molecule and a transmembrane protein, is overexpressed in non-small cell lung cancer (NSCLC), making it an attractive therapeutic target. Here, we aimed to systematically evaluate the value of B7-H3 as a target in NSCLC via T cells expressing B7-H3-specific chimeric antigen receptors (CARs) and bispecific killer cell engager (BiKE)-redirected natural killer (NK) cells. Methods We generated B7-H3 CAR and B7-H3/CD16 BiKE derived from an anti-B7-H3 antibody omburtamab that has been shown to preferentially bind tumor tissues and has been safely used in humans in early-phase clinical trials. Antitumor efficacy and induced-immune response of CAR and BiKE were evaluated in vitro and in vivo. The effects of B7-H3 on aerobic glycolysis in NSCLC cells were further investigated. Results B7-H3 CAR-T cells effectively inhibited NSCLC tumorigenesis in vitro and in vivo. B7-H3 redirection promoted highly specific T-cell infiltration into tumors. Additionally, NK cell activity could be specially triggered by B7-H3/CD16 BiKE through direct CD16 signaling, resulting in significant increase in NK cell activation and target cell death. BiKE improved antitumor efficacy mediated by NK cells in vitro and in vivo, regardless of the cell surface target antigen density on tumor tissues. Furthermore, we found that anti-B7-H3 blockade might alter tumor glucose metabolism via the reactive oxygen species-mediated pathway. Conclusions Together, our results suggest that B7-H3 may serve as a target for NSCLC therapy and support the further development of two therapeutic agents in the preclinical and clinical studies.

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B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

Cited by 177 publications

References 53 publications

Transcriptional landscape of PTEN loss in primary prostate cancer

Transcriptional landscape of PTEN loss in primary prostate cancer

Combinational Immunotherapy for Hepatocellular Carcinoma: Radiotherapy, Immune Checkpoint Blockade and Beyond

Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes

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