Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model

Area of Science:

• Immunology
• Oncology
• Gene Therapy

Background:

• T cell receptor (TCR) T cell therapy shows promise for cancer treatment.
• Developing effective TCR T cell therapies for epithelial cancers requires high-avidity TCRs targeting tumor-specific antigens.
• The human papillomavirus (HPV) E7 antigen is a potential target for HPV-positive cancers.

Purpose of the Study:

• To determine if genetically engineered TCR T cells targeting HPV E7 can induce regression of HPV-positive cancers.
• To identify and characterize a high-avidity TCR against HPV E7 for potential therapeutic applications.

Main Methods:

• Identified an HPV-16 E7-specific, HLA-A*02:01-restricted TCR from a patient with cervical intraepithelial neoplasia.
• Transduced human T cells to express the identified TCR.
• Evaluated TCR T cell function in vitro against HPV-16+ cancer cell lines and in vivo using a mouse model of HPV-16+ cervical cancer.

Main Results:

• The identified TCR demonstrated high functional avidity and CD8 coreceptor-independent tumor targeting.
• TCR-transduced T cells effectively recognized and killed HPV-16+ cervical and oropharyngeal cancer cell lines.
• Regression of established HPV-16+ human cervical cancer tumors was observed in a mouse model.

Conclusions:

• The study supports the therapeutic potential of TCR T cell therapy targeting HPV E7 for HPV-positive cancers.
• The findings provide a basis for a clinical trial of E7 TCR gene therapy in patients with metastatic HPV-positive cancers.