Engineering Cancer Cells with TNF-α Overexpression for Stronger T Cell Activation

Immunotherapy approaches consisting of genetically modified cancer cells used as cancer vaccines have become a promising platform for cancer treatment. Scientists at Creative Biolabs understand how to fully exploit this promising therapeutic approach. We provide you with engineering cancer cell line services according to your requirements. We can help you move your immunotherapy development to the next step.

Functions of TNF-α

Tumor necrosis factor alpha (TNF-α) is one of the essential pro-inflammatory cytokines. Broadly, TNF-α can activate pathways leading to three different cellular responses: cell survival and proliferation; transcription of pro-inflammatory genes; and cell death. As a pleiotropic cytokine, TNF-α has contradictory roles in oncoimmunology. On one hand, TNF activates the immune system to help kill cancer cells. On the other hand, TNF-α is also produced by tumors and can act as an endogenous tumor promoter to stimulate the growth, proliferation, invasion and metastasis, and tumor angiogenesis of cancer cells. TNF-α was the first cytokine to be employed for cancer treatment. However, TNF-α is limited due to its severe toxicity. Novel strategies have been considered aimed at exploiting the antitumor potential of this cytokine bypassing the systemic toxicity.

Cancer-suppressive properties of TNF-α. Fig.1 Cancer-suppressive properties of TNF-α. (Haabeth, et al., 2012)

Studies Performed with TNF-α Overexpressing Tumor Cells

Tumors have been genetically adapted to produce TNF with the intent of making them more immunogenic. Studies show methylcholanthrene (MCA)-induced murine sarcoma lines engineering with TNF-α overexpression showed a direct antitumor effect in vivo.

Engineering Cancer Cells with VEGF165 Overexpression Service

Genetically modified tumor cells releasing various cytokines have been shown to enhance tumor immunogenicity and induce the regression of preexisting tumors. In cancer immunology, TNF-α activates antigen-presenting cells and promotes the activation and proliferation of effector T cells. Therefore, scientists at Creative Biolabs are developing a novel strategy to genetically modify cancer cells to produce TNF-α and increase the killing of cancer cells, meanwhile bypassing systemic toxicity. We are able to use viral and non-viral vectors to achieve robust overexpression of TNF-α genes. A detailed protocol will be provided to customers.

Our R&D team is dedicated to helping our clients develop therapy approaches against various tumors. Our engineering cancer cell service can cover a variety of cancer cell lines (including adherent cells and suspension cells). The time required to generate a new stable cell line is from 1 to 3 months. It depends on the cell line and the overexpression system.

Other than TNF-α overexpression, we also can engineer cancer cells with other cytokines and regulators overexpression.

Creative Biolabs provides custom services upon request. If you have any special needs for this service, please contact us.

References

  1. Marincola, F.M.; et al. Treatment of established lung metastases with tumor-infiltrating lymphocytes derived from a poorly immunogenic tumor engineered to secrete human TNF-alpha. Journal of immunology. 1994, 152(7):3501-13.
  2. Haabeth, O.A.; et al. A model for cancer-suppressive inflammation. Oncoimmunology. 2012, 1(7):1146-55.

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