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High-grade glioma is one of the deadliest primary tumors of the central nervous system. Despite the many novel immunotherapies currently in development, it has been difficult to achieve breakthrough results in clinical studies. The reason may be due to the suppressive tumor microenvironment of gliomas that limits the function of specific immune cells (e.g., T cells) which are currently the primary targets of immunotherapy. However, tumor-associated macrophage, which are enriched in tumors, plays an important role in the development of GBM and is becoming a research hotspot for immunotherapy. This review focuses on current research advances in the use of macrophages as therapeutic targets or therapeutic tools for gliomas, and provides some potential research directions. [ABSTRACT FROM AUTHOR]

The therapeutic use of bispecific T‐cell engaging (BiTE) antibodies has shown great potential for treating malignancies. BiTE can simultaneously engage CD3ε on T cells and tumor antigen on cancer cells, thus exerting an effective antitumor effect. Nevertheless, challenges in production, manufacturing, and short serum half‐life of BiTE have dampened some of the promise and impeded the pace of BiTE‐based therapeutics to combat diseases. Nowadays, in vitro‐transcribed mRNA has achieved programmed production, which is more flexible and cost‐effective than the traditional method of producing recombinant antibody. Here, the authors have developed a BiTE‐based mRNA treatment by encapsulating mRNA encoding B7H3×CD3 BiTE into a novel ionizable lipid nanoparticles (LNPs). The authors have found that LNPs have high transfection efficiency, and the hepatosplenic targeting capability of produce high concentrations of BiTE. Above all, a single intravenous injection of BiTE mRNA‐LNPs could achieve high levels of protein expression in vivo and significantly prolonged the half‐life of the BiTE, which can elicit robust and durable antitumor efficacy against hematologic malignancies and melanoma. Therefore, their results suggested that the therapeutic strategy based on mRNA expression of B7H3×CD3 BiTE is of potential research value and has promising clinical application prospects. [ABSTRACT FROM AUTHOR]

A craniopharyngioma (CP) is a rare epithelial tumor of the sellar and parasellar region. CPs are difficult to treat due to their anatomical proximity to critical nervous structures, which limits the ability of the surgeon to completely resect the lesion, exposing patients to a high risk of recurrence. The treatment of craniopharyngiomas is primarily surgery and radiotherapy. So far, neither a cell line nor an animal model has been established, and thus data on other treatment options, such as chemotherapy and immunotherapy, are limited. Here, the expression profile of the pan-cancer antigen B7-H3 in various cancer types including CP was examined by immunohistochemistry. An in vitro organoid model was established by using fresh tissue biospecimens of CP. Based on the organoid model, we evaluated the antitumor efficacy of B7-H3-targeted immunotherapy on CP. As a result, the highest expression of B7-H3 was observed in CP tissues across various cancer types. Although B7-H3-targeted chimeric antigen-receptor T cells show obvious tumor-killing effects in the traditional 2D cell culture model, limited antitumor effects were observed in the 3D organoid model. The B7-H3-targeted antibody-DM1 conjugate exhibited a potent tumor suppression function both in 2D and 3D models. In conclusion, for the first time, we established an organoid model for CP and our results support that B7-H3 might serve as a promising target for antibody-drug conjugate therapy against craniopharyngioma. [ABSTRACT FROM AUTHOR]

Objective: We conducted a first‐in‐human study to evaluate the bioactivity and safety of B7‐H3‐targeted chimeric antigen receptor (CAR) autologous T cells for treating recurrent anaplastic meningioma. Methods: Tumor tissues from a patient with recurrent anaplastic meningioma were evaluated for B7‐H3 expression. B7‐H3‐targeted CAR‐T cells were delivered into the intracranial tumor resection cavity using an Ommaya device at a maximum dose of 1.5 × 107 cells. Magnetic resonance imaging (MRI) screening and multiple serum indexes were regularly monitored. The patient received surgical intervention after three‐cycle infusions, allowing analysis for CAR‐T‐cell infiltration and target antigen expression in post‐CAR‐T therapy tumor tissues. Results: Immunochemical analysis demonstrated high and homogeneous B7‐H3 expression in tumor samples. MRI results indicated that the tumor near the delivery device was relatively stable compared with the rapid progression of tumors distant from the device. We found CAR‐T‐cell trafficking to regions of B7‐H3+ tumor tissues near the device, but not to tumor tissues distant from the device. Decreased B7‐H3 expression was observed near the region of CAR‐T‐cell infiltration after therapy. The intracavitary delivery of B7‐H3‐targeted CAR‐T cells was well‐tolerated and not associated with any toxic effects of grade 3 or higher. Conclusion: Our results suggested that although intracavitary administration of B7‐H3‐targeted CAR‐T cells was safe and resulted in local bioactivity, addressing antigen loss and CAR‐T‐cell trafficking may further enhance the applications of B7‐H3‐targeted CAR‐T‐cell therapy. [ABSTRACT FROM AUTHOR]

Craniopharyngiomas (CPs) are uncommon intracranial benign neoplasms that located in sellar/parasellar region with clinically challenging. B7-H3 is an immune checkpoint molecule highly expressed in many malignant tumors. In this study, we analyzed whether B7-H3 is expressed in 44 CPs samples (adamantinomatous CPs: n = 30 and papillary CPs: n = 14), and whether it could serve as an immunotherapy target in CPs. Immunohistochemical analysis showed that B7-H3 was highly expressed in adamantinomatous CPs (184.3 ± 13.58) and papillary CPs (223.2 ± 11.89), while almost undetectable in normal brain tissue (24 ± 4.9). Besides, B7-H3 expression level was correlated with poor prognosis of patients with CPs. Immunofluorescence and Western blot analysis further suggested that β-catenin co-localized with B7-H3 and could promote its expression in adaCPs. B7-H3 expression level was positively correlated with staining intensity of IBA1+ cells, but negatively with T cell infiltration in CPs, suggesting that B7-H3 might play a role in the regulation of tumor microenvironment in CPs. Moreover, B7-H3/CD3 bi-specific T cell engager (BiTE) efficiently inhibited the growth of human primary craniopharyngioma cells in a time- and dose-dependent manner. Our results revealed B7-H3 was highly expressed in CPs and targeting B7-H3 might therefore be an effective therapeutic strategy against craniopharyngioma. • B7-H3 is highly overexpressed in craniopharyngioma (CP) samples. • Higher expression of B7-H3 is correlated with poor prognosis in patients with CP. • B7-H3/CD3 bispecific T cell engager efficiently kills B7-H3 overexpressed CP cells. [ABSTRACT FROM AUTHOR]