Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47Δ combination therapy against glioblastoma

Chalise, Lushun; Kato, Akira; Ohno, Masasuke; Maeda, Sachi; Yamamichi, Akane; Kuramitsu, Shunichiro; Shiina, Satoshi; Takahashi, H.; Ozone, Sachiko; Yamaguchi, Junya; Kato, Yoshinori; Rockenbach, Yumi; Natsume, Atsushi; Todo, Tomoki

doi:10.1016/j.omto.2022.07.006

Cited by 53 publications

(40 citation statements)

References 45 publications

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“…Vaccines containing glioma-associated antigens or dendritic cells loaded with mRNA or tumor lysate have been used to treat primary brain tumors, and they may work in tandem with CAR T therapy to overcome tumor heterogeneity and induce an endogenous immune response [ 187 ]. A combination of anti-podoplanin CAR T cells with oncolytic herpes virus G47D successfully reduced ‘on-target off tumor’ toxicity acting against patient-derived glioma stem cells while sparing normal cells [ 188 ].…”

Section: Perspectives and Critical Analysesmentioning

confidence: 99%

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CAR T cells: engineered immune cells to treat brain cancers and beyond

et al. 2023

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Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential targets for immunotherapy-based targeting, including but not limited to EGFRvIII, IL13Rα2, and HER2. The outstanding clinical responses to CAR T cell-based treatments in patients with hematological malignancies have generated interest in using this approach to treat solid tumors. Research results to date support the astounding clinical response rates of CD19-targeted CAR T cells, early clinical experiences in brain tumors demonstrating safety and evidence for disease-modifying activity, and the promise for further advances to ultimately assist patients clinically. However, several variable factors seem to slow down the progress rate regarding treating brain cancers utilizing CAR T cells. The current study offers a thorough analysis of CAR T cells’ promise in treating brain cancer, including design and delivery considerations, current strides in clinical and preclinical research, issues encountered, and potential solutions.

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Section: Perspectives and Critical Analysesmentioning

confidence: 99%

“…A combination of anti-podoplanin CAR T cells with oncolytic herpes virus G47D successfully reduced 'on-target off tumor' toxicity acting against patient-derived glioma stem cells while sparing normal cells [188].…”

Section: Perspectives and Critical Analysesmentioning

confidence: 99%

CAR T cells: engineered immune cells to treat brain cancers and beyond

et al. 2023

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“…CD44v3-10 ORF was obtained from the RIKEN BRC through the National Bio-Resource Project of the MEXT, Japan. CD44s and CD44v3-10 cDNAs were subcloned into pCAG-Ble-ssPA16 vector possessing signal sequence and N-terminal PA16 tag (GLEGGVAMPGAEDDVV) [19,[45][46][47][48], which is detected by NZ-1 [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. CHO/CD44s and CHO/CD44v3-10 were established by transfecting pCAG-Ble/PA16-CD44s and pCAG-Ble/PA16-CD44v3-10 into CHO-K1 cells using a Neon transfection system (Thermo Fisher Scientific, Inc.).…”

Section: Cell Linesmentioning

confidence: 99%

Development of a Novel Anti-CD44 variant 6 Monoclonal Antibody for Multiple Applications against Colorectal Carcinomas

Ejima¹,

Suzuki²,

Tanaka³

et al. 2023

Preprint

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CD44 is a cell surface glycoprotein, and its isoforms are produced by the alternative splicing with the standard and variant exons. The CD44 variant exon containing isoforms (CD44v) are overexpressed in carcinomas. CD44v6 is one of the CD44v, and its overexpression predicts poor prognosis in colorectal cancer (CRC) patients. CD44v6 plays critical roles in CRC adhesion, proliferation, stemness, invasiveness, and chemoresistance. Therefore, CD44v6 is a promising target for cancer diagnosis and therapy for CRC. In this study, we established anti-CD44 monoclonal antibodies (mAbs) by immunizing mice with CD44v3-10-overexpressed Chinese hamster ovary-K1 (CHO) cells. We then characterized them using enzyme-linked immunosorbent assay, flow cytometry, western blotting, and immunohistochemistry. One of the established clones (C44Mab-9; IgG1, kappa) reacted with a peptide of variant 6-encoded region, indicating that C44Mab-9 recognizes CD44v6. Furthermore, C44Mab-9 reacted with CHO/CD44v3-10 cells or CRC cell lines (COLO201 and COLO205) by flow cytometry. The apparent KD of C44Mab-9 for CHO/CD44v3-10, COLO201, and COLO205 was 8.1 × 10−9 M, 1.7 × 10−8 M, and 2.3 × 10−8 M, respectively. C44Mab-9 detected the CD44v3-10 in western blotting, and partially stained the formalin-fixed paraffin-embedded CRC tissues in immunohistochemistry. Collectively, C44Mab-9 is useful for detecting CD44v6 in various applications.

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“…In a study, Lp2 CAR-T cells were designed to target PDPN-expressing glioma cells to exclude normal PDPN-expressing cells. Concurrent use of Lp2 CAR-T and third-generation recombinant herpes simplex virus-1 lytic virus G47Δ further inhibited tumor growth and improved survival [ 377 ].…”

Section: Solid Tumormentioning

confidence: 99%

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

Zhang

Cao

et al. 2022

Mol Cancer

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Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

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Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47Δ combination therapy against glioblastoma

Cited by 53 publications

References 45 publications

CAR T cells: engineered immune cells to treat brain cancers and beyond

CAR T cells: engineered immune cells to treat brain cancers and beyond

Development of a Novel Anti-CD44 variant 6 Monoclonal Antibody for Multiple Applications against Colorectal Carcinomas

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

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