Cell-based molecularly targeted therapy: targeting oncoproteins with T cell receptor gene therapy

Hinrichs, Christian S.

doi:10.1172/jci120386

Cited by 3 publications

(2 citation statements)

References 17 publications

(16 reference statements)

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“…Expanded tumor infiltrating lymphocytes (TILs) or TCR engineered T-lymphocyte cellular therapies show promise in the treatment of solid tumors such as squamous cell carcinomas [15,16], but have significant drawbacks. These include the need for lymphodepleting conditioning chemotherapy before infusion, post-infusion IL-2 that can cause capillary leak syndrome and cytokine storm, and HLA-restriction for MHC-restricted Tlymphocyte antigens [17].…”

Section: Discussionmentioning

confidence: 99%

Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells

et al. 2019

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High affinity natural killer cells (haNKs) are a cell therapy product capable of mediating both direct and antibody-dependent cell-mediated cytotoxicity (ADCC). These cells may be particularly useful in tumors that escape T-cell anti-tumor immunity by harboring antigen processing and presentation defects. Here, we demonstrated that haNKs directly kill both HPV-positive and negative head and neck squamous cell carcinoma cells. Variable tumor cell sensitivity to haNK direct cytotoxicity did not correlated with MHC class I chain-related protein A or B (MICA or MICB) expression. Importantly, haNK killing was significantly enhanced via ADCC mediated by cetuximab or avelumab in cells with higher baseline EGFR or PD-L1 expression, respectively. The ability of IFNγ to induce tumor cell PD-L1 expression correlated with enhanced PD-L1-specific ADCC. IFNγ induced neither tumor cell EGFR expression nor EGFR-specific ADCC. Although a single dose of 8Gy IR did not appear to directly enhance susceptibility to haNK killing alone, enhanced PD-L1-and EGFR-mediated ADCC after IR correlated with increased PD-L1 and EGFR expression in one of four models. This pre-clinical evidence supports the investigation of haNK cellular therapy in combination with ADCC-mediating mAbs, with or without IR, in the clinical trial setting for patients with advanced HNSCCs. Given the MHC-unrestricted nature of this treatment, it may represent an opportunity to treat patients with non-T-cell inflamed tumors.

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Section: Discussionmentioning

confidence: 99%

Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells

et al. 2019

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“…These stress-induced oncoproteins may be responsible for imparting resistance to therapy, relapse, and metastasis. Targeting these stress-induced oncoproteins by various means has been an important goal in medical research [35] . As oncoproteins may serve as TAAs, we chose a unique and specific immune approach using synthetic peptides of CD151 as tumour vaccines.…”

Section: Discussionmentioning

confidence: 99%

Peptides of tetraspanin oncoprotein CD151 trigger active immunity against primary tumour and experimental lung metastasis

Lin

Chen

et al. 2019

eBioMedicine

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a b s t r a c tBackground: Active immunotherapy is an effective, long-lasting, cheap, and safe approach to suppress cancer progression; however, the key issue is to develop appropriate tumour vaccines. Oncoproteins are up-regulated under various stress conditions and promote cell survival. Oncoproteins and their immunogenic domains could serve well as tumour vaccines and prime the hosts' active anti-tumour immunity. Methods: Proteomic and bioinformatic analyses were performed to identify potential tumour associated antigens (TAAs). Then, peptides derived from CD151 were designed and synthesized according to the major histocompatibility complex (MHC) I binding and immunogenicity. Cytotoxicity assay, flow cytometry, immunohistochemistry, and in vivo bioluminescence imaging were performed to assess the active antitumour immunity triggered by CD151 peptides in H22 primary hepatoma and experimental 4T1 breast cancer lung metastasis models. Findings: CD151 was identified as an ideal TAA based on proteomic and bioinformatic analyses. CD151 peptides as tumour vaccines triggered active anti-tumour immunity against H22 hepatoma and the lung metastasis of 4T1 breast cancer in two mouse models through the activation of CD8 + IFN γ + lymphocytes and the subsequent targeted cytotoxicity. Further, the peptides suppressed the negative regulators, myeloid-derived suppressor cells. Survival was prolonged for mice with lung metastases from CD151 peptide-immunised groups. Interpretation: The up-regulated oncoproteins in 8 Gy-irradiated tumour cells are good candidates for designing immunogenic peptides as tumour vaccines. Anti-tumour active immunity primed by peptides from CD151 may be an effective and safe approach to suppress cancer progression. Implications of all the available evidenceAnti-tumour active immunity primed by peptides from oncoproteins/TAAs could serve as an effective, long-lasting, cheap, and safe way to suppress cancer progression.

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Neoantigen-targeted TCR-T cell therapy for solid tumors: How far from clinical application

Zhu

et al. 2022

Cancer Letters

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Cell-based molecularly targeted therapy: targeting oncoproteins with T cell receptor gene therapy

Cited by 3 publications

References 17 publications

Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells

Direct and antibody-dependent cell-mediated cytotoxicity of head and neck squamous cell carcinoma cells by high-affinity natural killer cells

Peptides of tetraspanin oncoprotein CD151 trigger active immunity against primary tumour and experimental lung metastasis

Neoantigen-targeted TCR-T cell therapy for solid tumors: How far from clinical application

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