Lm-LLO-Based Immunotherapies and HPV-Associated Disease

Area of Science:

• Oncology
• Immunology
• Microbiology

Background:

• Human papillomavirus (HPV) infection is a primary cause of cervical and other cancers.
• Cellular immunity targeting HPV oncoproteins E6 and E7 can resolve HPV-associated neoplasia.
• Novel immunotherapy platforms are needed to effectively combat HPV-driven malignancies.

Purpose of the Study:

• To introduce a novel live attenuated Listeria monocytogenes (Lm)-based immunotherapy, ADXS11-001, for HPV-associated diseases.
• To describe the mechanism of action of ADXS11-001, which involves secretion of an Lm-LLO-E7 fusion protein.
• To highlight the ongoing clinical evaluation of ADXS11-001 in Phase 2 trials.

Main Methods:

• Development of ADXS11-001, a genetically engineered live attenuated Lm strain.
• Engineering of the Lm-LLO-E7 fusion protein to deliver HPV-16 E7 antigen and LLO adjuvant.
• Preclinical testing in relevant models to assess immune stimulation and therapeutic efficacy.
• Phase 2 clinical trials in patients with cervical intraepithelial neoplasia, cervical cancer, and HPV-positive head and neck cancer.

Main Results:

• Preclinical studies demonstrated that the Lm-LLO-E7 construct stimulates immune responses.
• The immunotherapy construct showed potential for affecting therapeutic outcomes in preclinical models.
• ADXS11-001 is currently under investigation in human clinical trials for specific HPV-related cancers.

Conclusions:

• Live attenuated bacterial immunotherapy, exemplified by ADXS11-001, offers a complex and potentially highly effective strategy against HPV-driven cancers.
• The evolved host-pathogen interaction with Lm provides a robust platform for inducing potent, conserved, and non-tolerant immune mechanisms.
• ADXS11-001 represents a promising novel immunotherapy for HPV-associated malignancies, leveraging unique immunological pathways.