GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction

Sujjitjoon, Jatuporn; Sayour, Elias; Tsao, Shih-Ting; Uiprasertkul, Mongkol; Sanpakit, Kleebsabai; Buaboonnam, Jassada; Yenchitsomanus, Pa‐thai; Atchaneeyasakul, La-ongsri; Chang, Lung‐Ji

doi:10.1016/j.tranon.2020.100971

Cited by 22 publications

(11 citation statements)

References 42 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 43 Research and development of NB tumor therapy has focused on GD2, including GD2 antibodies and GD2 CAR-T cells. 44 Many of these studies have exhibited powerful anticancer abilities in animal models. Among them, the anti-GD2 monoclonal antibody dinutuximab (ch14.18) has been approved by the US Food and Drug Administration, and dinutuximab β (ch14.18/CHO) has been approved by the European Medicines Agency for high-risk neuroblastoma treatment.…”

Section: Discussionmentioning

confidence: 99%

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

Zhang¹,

Wang²,

Zhu³

et al. 2021

IJN

View full text Add to dashboard Cite

Background: GD2 is a mainstream biomarker for neuroblastoma (NB)-targeted therapy. Current anti-GD2 therapeutics exhibit several side effects since GD2 is also expressed at low levels on normal cells. Thus, current anti-GD2 therapeutics can be compromised by the coexistence of the target receptor on both cancer cells and normal cells. Propose: Aptamers are promising and invaluable molecular tools. Because of the pH difference between tumor and normal cells, in this study, we constructed a pH-sensitive aptamer-mediated drug delivery system (IGD-Targeted). Methods: In vivo Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to generate a novel GD2 aptamer. Flow cytometry and molecular docking were applied to assess the binding specificities, affinities abilities of the aptamers. Confocal microscope, CCK8 assay, and BrdU assay were utilized to evaluate whether IGD-Targeted could only bind with GD2 at acidic environment. To evaluate whether IGD-Targeted could inhibit GD2-positive tumor and protect normal cells, in vivo living imaging, histomorphological staining, blood test, and RNA-sequencing were observed in animal model. Results: GD2 aptamer termed as DB67 could bind with GD2-positive cells with high specificity, while has minimal cross-reactivities to other negative cells. It has been validated that the i-motif in IGD-Targeted facilitates the binding specificity and affinity of the GD2 aptamer to GD2-positive NB tumor cells but does not interfere with GD2-positive normal cells at the pH of the cellular microenvironment. In addition, IGD-Targeted is capable of delivering Dox to only GD2-positive NB tumor cells and not to normal cells in vivo and in vitro, resulting in precise inhibition of tumor cells and protection of normal cells. Conclusion:This study suggests that IGD-Targeted as a promising platform for NB therapy which could show greater tumor inhibition and fewer side effects to normal cells, regardless of the existence of the same receptor on the target and nontarget cells.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

Zhang¹,

Wang²,

Zhu³

et al. 2021

IJN

View full text Add to dashboard Cite

show abstract

“…Subsequently, others developed local immunotherapy formulations also based on anti-GD2 CART cells, including an injectable hydrogel to prolong their localization at the site of injection. After IVi administration, the formulation resulted in complete tumor response and no recurrence or ocular toxicity in orthotopic xenograft models (137,138) (Figure 2).…”

Section: Gangliosides and Other Targets For Immunotherapymentioning

confidence: 97%

Treatment of Retinoblastoma: What Is the Latest and What Is the Future

et al. 2022

View full text Add to dashboard Cite

The management of retinoblastoma, the most common intraocular malignancy in children, has changed drastically over the last decade. Landmark developments in local drug delivery, namely, safer techniques for intravitreal chemotherapy injection and ophthalmic artery chemosurgery, have resulted in eye globe salvages that were not previously attainable using systemic chemotherapy or external beam irradiation. Novel drugs, oncolytic viruses, and immunotherapy are promising approaches in the treatment of intraocular retinoblastoma. Importantly, emerging studies of the pattern of tumor dissemination and local drug delivery may provide the first steps toward new treatments for metastatic disease. Here, we review recent advances in retinoblastoma treatment, especially with regard to local drug delivery, that have enabled successful conservative management of intraocular retinoblastoma. We also review emerging data from preclinical and clinical studies on innovative approaches that promise to lead to further improvement in outcomes, namely, the mechanisms and potential uses of new and repurposed drugs and non-chemotherapy treatments, and discuss future directions for therapeutic development.

show abstract

“…Earlier clinical studies have shown CAR T-cell therapy to be effective against RB. U pon co- culturing with GD2-antigen and GD2-CAR T cells, nearly 80% of RB cells died in 24 h, and approximately 100% cell mortality was achieved in 3 days ( 24 ).…”

Section: Retinoblastomamentioning

confidence: 99%

The immunotherapy advancement targeting malignant blastomas in early childhood

Zang

Ding²,

Liu³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

Malignant blastomas develop relentlessly in all functional body organs inflicting severe health ailments in younger children. Malignant blastomas exhibit diverse clinical characteristics in compliance with their emergence in functional body organs. Surprisingly, neither of these preferred treatment types (surgery, radiotherapy, and chemotherapy) showed promise or were effective in treating malignant blastomas among child patients. N ew, innovative immunotherapeutic procedures including monoclonal antibodies and chimeric-antigen based receptor (CAR) cell therapy, coupled with the clinical study of reliable therapeutic targets and immune regulatory pathways targeting malignant blastomas, have attracted the attention of clinicians recently.

show abstract

GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction

Cited by 22 publications

References 42 publications

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

Treatment of Retinoblastoma: What Is the Latest and What Is the Future

The immunotherapy advancement targeting malignant blastomas in early childhood

Contact Info

Product

Resources

About