Engineering Cancer Cells with TGF-beta Overexpression for Stronger T Cell Activation
TGF-β signaling blockade has proven to be efficient in preventing the development of a variety of tumor types and has led to the development of vaccines targeting the production of TGF-β. Supported by advanced technology and dedicated research teams, Creative Biolabs provides services to generate TGF-β gene-modified cancer cell lines based on our client requirements and project specifications.
TGFβ Functions in T cell Activation
Transforming growth factor beta (TGF-β) is a multipotent immunosuppressive cytokine and plays an integral role in regulating immune responses. In cancer, TGF-β has been shown to support the evasion of cancer cells from immune surveillance and to contribute to the subversion of the immune system from being an extrinsic tumor suppressor to a promoter of malignant growth and spread.
TGF-β has sweeping inhibitory effects on the immune system, negatively affecting many immune cell types and functions, including:
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Inhibition of CD8+T cells functions like target recognition, cytotoxicity, and proliferation
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Inhibition of the proliferation of T cells
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Inhibition o the differentiation of both CD4+ and CD8+ naive T cells into effectors
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Suppression of effector Th cell differentiation
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Conversion of naïve T cells into regulatory T cells
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Inhibition of the proliferation of B cells
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Inhibition of the production of proinflammatory cytokines from macrophages, B cells, and T cells
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Suppression of macrophages, dendritic cells (DCs) and natural killer (NK) cells
Fig.1 Immunobiologic effects of TGF-β. (van den Bulk, et al., 2021)
Studies Performed with Engineered Liver Cancer Cells
The development of therapies based on inhibiting the TGF-β pathway might be a feasible strategy to enhance the efficacy of immunotherapy. Some studies were trying to reverse the effects of immunosuppression in host cells and increase anti-tumor immunity by modifying TGF-β anti-sense molecules into cancer cell lines.
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A phase I clinical trial showed TGF-β antisense-modified autologous tumor cells induced humoral and cellular immunity in patients with advanced glioma.
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A phase II clinical trial showed a TGF-β2 antisense gene-modified allogeneic tumor vaccine demonstrated enhancement of tumor antigen recognition and confirmed their efficacy and safety in advanced non-small cell lung cancer (NSCLC) patients.
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A study indicated immunization with TGF-β antisense oligonucleotide-modified autologous tumor vaccine enhanced the antitumor immunity in the murine bladder cancer model.
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A study showed the successful treatment of hepatocellular carcinoma tumors in rats by a hepatocellular carcinoma vaccine genetically altered with antisense TGF-β2.
Engineering Cancer Cells with TGF-β Overexpression Service
Based on advanced technology and dedicated research teams, Creative Biolabs has developed an optimized cancer cell engineering platform, turning cancer cells against themselves. We have standard and custom services to generate genetically modified tumor cells by suppressing their TGF-beta secretion with an antisense strategy. The generation of gene-modified cell lines can be time-consuming and complicated, especially for researchers unfamiliar with the process. Many of our oncology team members have rich experience in constructing an effective cell line. We assist in selecting the appropriate gene delivery technologies, optimized vector design and function verification services for your project. We are pleased to discuss your experimental details to help generate accurate price quotes and timeline estimates.
Our cell engineering services cover a range of different cancer cell lines, including:
Service Procedure
Creative Biolabs provides pharma/biotechnology research services for pharmaceutical, biotechnology, and academic institutions worldwide. Our scientists work as an extension of your development team, offering customized support to meet your project needs. Contact us to discuss your upcoming oncology study.
Reference
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van den Bulk, J.; et al. Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression. Clinical Science. 2021, 135(1): 35-52.
For Research Use Only | Not For Clinical Use