The safety and efficacy of ADXS11-001 with or without chemotherapy in patients with recurrent cervix cancer who have failed prior cytotoxic treatment

U. Venkatesh1*, Sri Rama Radha1, P. Suresh1, G. Sravan Reddy2
1St John’s College of Pharmacy, Yemmiganur, Kurnool, Andhra Pradesh
2Hi-Q Herbals, Kothapet, Hyderabad, Telangana

A B S T R A C T
Cervical cancer, cancer in cervix the lower part of the uterus that opens at the top of vagina. It is one of the most fatal diseases that affect the women in majority of cases all over the world. It is the third most common type of cancer. Main cause for the cervix cancer is infection with Human Papilloma Virus (HPV). The viral oncoprotein E₆ complexes with Tumour Inhibitor Gene (p⁵³) and E₇ complexes with Tumour Suppressor Protein Retinoblastoma (p^Rb). This disrupts the cell cycle regulation leading to genomic instability and causes subsequent neoplasia. Conventional therapies for cancer such as chemotherapy and radiotherapy are characterized by poor survival rates due to tumour development of drug resistance and lack of tumour specificity resulting in undesirable side effects on healthy cells. Hence an alternate method of vaccination is preffered here. ADXS11-001 is a live attenuated vaccine consisting of Listeria monocytogenes(Lm) bacteria. It is bio-engineered to make it less likely to cause infection to make a special substance called E₇. Bio-engineered to secrete an antigen- adjuvant fusion protein consisting of a truncated fragment of Lm- Listeriolysin (LLO) fused to HPV-16-E₇. LLO permits bacteria to escape from phagosomes and to live intracellularly. This potentiates the class-I & II MHC antigen- processing pathway leading to specific CD₄ and CD₈ T- cell responses. Thus the drug shows it action on immune responses. ADXS11-001 was found to cause the therapeutic regression of tumours that express the HPV-16- E_7. Cisplatin is the most effective drug in cervical cancer treatment. ADXS11-001 alone & ADXS11-001 in combination with cisplatin is also administered to patients. Combination showed the better efficacy results than ADXS11-001 alone.
Keywords: Cervical cancer, Human Papilloma Virus, Viral Oncoprotein, Tumour Inhibitor gene, Tumour suppressor protein Retinoblastoma, ADXS11-001, Listeria monocytogenes, Listeriolysin, Phagosomes, Cisplatin.