Antibody-mediated p53 protein therapy prevents liver metastasis in vivo

Area of Science:

• Oncology
• Molecular Biology
• Immunotherapy

Background:

• The tumor suppressor protein p53 plays a critical role in cancer prevention.
• Effective delivery of full-length p53 protein into cancer cells remains a challenge for therapeutic applications.

Purpose of the Study:

• To evaluate the efficacy of a novel Fv-p53 fusion protein, mediated by monoclonal antibody (mAb) 3E10 Fv, for cancer therapy.
• To assess the in vitro and in vivo anti-cancer effects of Fv-p53 on colon cancer metastasis.

Main Methods:

• An Fv-p53 fusion protein was produced in Pichia pastoris.
• In vitro studies utilized CT26.CL25 colon cancer cells to assess cell killing and p53 intracellular transport.
• In vivo experiments involved a mouse model of colon cancer liver metastasis, with Fv-p53 administered via splenic injection.

Main Results:

• Fv-p53 fusion protein demonstrated selective killing of CT26.CL25 cells, while Fv or p53 alone had no effect.
• Immunohistochemical staining confirmed Fv's role in facilitating p53 transport into cells.
• In vivo, Fv-p53 treatment significantly reduced liver metastasis scores in mice compared to controls (0.8 vs. 3.3, P=0.004).

Conclusions:

• Fv-p53 fusion protein therapy is effective in preventing and treating colon cancer liver metastasis in a mouse model.
• mAb 3E10 Fv serves as a crucial mediator for intracellular and intranuclear delivery of p53.
• This study represents a significant advancement in p53 protein therapy for cancer metastasis.