Strategies to Improve Chimeric Antigen Receptor Therapies for Neuroblastoma

Sawaisorn, Piamsiri; Atjanasuppat, Korakot; Anurathapan, Usanarat; Hongeng, Suradej

doi:10.3390/vaccines8040753

Cited by 10 publications

(9 citation statements)

References 197 publications

(257 reference statements)

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“…Although the adhesion molecule L1-CAM has been targeted for neuroblastoma in both preclinical and clinical studies, GD2 is unquestionably the leading antigenic target investigated for the development of CAR-T cells due to its high expression in the tumor [ 57 ]. Multiple clinical trials are underway using second- and third-generation GD2-specific CARs incorporating different signaling costimulatory molecules into the construct (Table 1 ).…”

Section: Car-t Cells For Pediatric Solid Tumors—a Clinical Experiencementioning

confidence: 99%

CAR-T Therapies in Solid Tumors: Opportunities and Challenges

et al. 2023

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Purpose of Review This review will discuss the challenges facing chimeric antigen receptor (CAR)-T cell application for solid tumors and opportunities to overcome these obstacles. In addition, this review will examine therapies that are in development for pediatric solid tumors. Recent Findings The similar success of CAR-T cell treatment for hematological malignancies has not been observed in solid tumors because of the hostile tumor microenvironment and tumor heterogeneity. Most strategies developed to combat these limitations emphasize combinatorial techniques that still require further testing. Preliminary results of multiple clinical trials, including GD2- and HER2-CAR-T cells, are encouraging but must be reproduced and validated on a larger scale. Summary CAR-T cell application in solid tumors remains challenging, and most research is in development. Several clinical trials are ongoing for pediatric solid tumors. Early results are promising but demonstrate the need for CAR-T cell modification to prevent tumor recurrence.

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Section: Car-t Cells For Pediatric Solid Tumors—a Clinical Experiencementioning

confidence: 99%

CAR-T Therapies in Solid Tumors: Opportunities and Challenges

et al. 2023

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“…The other challenge is the diverse immune-suppressive mechanisms exerted by the cancer microenvironment. How to overcome such adversity remains to be solved [99].…”

Section: Future Prospectivementioning

confidence: 99%

Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma

Chan

2022

Biomolecules

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Neuroblastoma is one of the few childhood cancers that carries a tumor-specific antigen in the form of a glycolipid antigen known as GD2. It has restricted expression in normal tissue, such as peripheral afferent nerves. Monoclonal antibodies targeting GD2 have been applied clinically to high-risk neuroblastoma with significant success. However, there are different anti-GD2 products and administration regimens. For example, anti-GD2 has been used in combination with chemotherapy during the induction phase or with retinoic acid during the maintenance stage. Regimens also vary in the choice of whether to add cytokines (i.e., IL-2, GMCSF, or both). Furthermore, the addition of an immune enhancer, such as β-glucan, or allogeneic natural killer cells also becomes a confounder in the interpretation. The question concerning which product or method of administration is superior remains to be determined. So far, most studies agree that adding anti-GD2 to the conventional treatment protocol can achieve better short- to intermediate-term event-free and overall survival, but the long-term efficacy remains to be verified. How to improve its efficacy is another challenge. Late relapse and central nervous system metastasis have emerged as new problems. The methods to overcome the mechanisms related to immune evasion or resistance to immunotherapy represent new challenges to be resolved. The newer anti-GD2 strategies, such as bispecific antibody linking of anti-GD2 with activated T cells or chimeric antigen receptor T cells, are currently under clinical trials, and they may become promising alternatives. The use of anti-GD2/GD3 tumor vaccine is a novel and potential approach to minimizing late relapse. How to induce GD2 expression from tumor cells using the epigenetic approach is a hot topic nowadays. We expect that anti-GD2 treatment can serve as a model for the use of monoclonal antibody immunotherapy against cancers in the future.

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“…156 This suggested that HER-2-targeted CAR-T cells might be suitable for the treatment of advanced HER-2+ GC, although their toxicity and immunogenicity will have to be verified in future trials. 156,[243][244][245] Furthermore, the focus of future studies would be to improve the antitumor activity of HER-2 targeted CAR-T cells by improving their proliferation capacity, function and persistence.…”

Section: Advances In Her-2-targeted Car-t Cell Therapy For Gcmentioning

confidence: 99%

From Anti-HER-2 to Anti-HER-2-CAR-T Cells: An Evolutionary Immunotherapy Approach for Gastric Cancer

Sun¹,

Li²,

Chen³

et al. 2022

JIR

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Current Therapeutic modalities provide no survival advantage to gastric cancer (GC) patients. Targeting the human epidermal growth factor receptor-2 (HER-2) is a viable therapeutic strategy against advanced HER-2 positive GC. Antibody-drug conjugates, small-molecule tyrosine kinase inhibitors (TKIs), and bispecific antibodies are emerging as novel drug forms that may abrogate the resistance to HER-2-specific drugs and monoclonal antibodies. Chimeric antigen receptor-modified T cells (CAR-T) targeting HER-2 have shown considerable therapeutic potential in GC and other solid tumors. However, due to the high heterogeneity along with the complex tumor microenvironment (TME) of GC that often leads to immune escape, the immunological treatment of GC still faces many challenges. Here, we reviewed and discussed the current progress in the research of anti-HER-2-CAR-T cell immunotherapy against GC.

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Strategies to Improve Chimeric Antigen Receptor Therapies for Neuroblastoma

Cited by 10 publications

References 197 publications

CAR-T Therapies in Solid Tumors: Opportunities and Challenges

CAR-T Therapies in Solid Tumors: Opportunities and Challenges

Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma

From Anti-HER-2 to Anti-HER-2-CAR-T Cells: An Evolutionary Immunotherapy Approach for Gastric Cancer

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