Good practice production and safety evaluation of the TERAH-7 recombinant protein: a step forward on technological development of a therapeutic vaccine to HPV-related cervical cancer

• Grant number: 23/00545-9
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Duration: June 01, 2023 - May 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Bruna Felício Milazzotto Maldonado Porchia Ribeiro
• Grantee: Bruna Felício Milazzotto Maldonado Porchia Ribeiro
• Host Company: Imunotera Soluções Terapêuticas Ltda. - EPP
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: São Paulo
• Associated researchers: Bianca da Silva Almeida ; Luis Carlos de Souza Ferreira
• Associated scholarship(s): 23/09127-5 - Good practice production and safety evaluation of the TERAH-7 recombinant protein: a step forward in the technological development of a therapeutic vaccine against Cervical Cancer caused by HPV, BP.PIPE

Abstract

Human papillomavirus (HPV) is the etiological agent of the most common sexually transmitted infection. Most infections are asymptomatic and are usually eliminated by the immune system, without any intervention. However, persistent HPV infections can lead to cervical intraepithelial neoplasia (CINs) and uterine cervix cancer, in addition to other types of cancer such as oropharyngeal and penile cancer. Available therapeutic interventions cause considerable side effects without necessarily significant efficacy. In this context, ImunoTera Soluções Terapeuticas has developed a therapeutic vaccine that teaches the immune system to recognize NICs and tumors caused by HPV. This vaccine is based on a recombinant hybrid protein (TERAH-7) that induces control of tumors associated with HPV-16 in the murine model. When TERAH-7 was associated with cisplatin, the most widely used chemotherapeutic agent to treat cervical cancer, it induced superior therapeutic efficacy compared to ImunoTera's main competitors strategies. In this scenario, the present proposal intends to advance the technological development of TERAH-7 through the production of batches of this protein under regulated conditions and the application in preclinical studies of chronic toxicity and reproductive toxicity, for safety evaluation. TERAH-7 batches will also be validated for stability and purity required for injectable products, in vitro biological activity, immunogenicity and therapeutic efficacy in the experimental model of tumors associated with HPV-16. These steps will help to qualify the product to application in a phase I/II clinical study in patients with high-grade CIN or cervical cancer induced by HPV in the future. If the therapeutic potential of TERAH-7 is confirmed in humans, the chances of licensing the technology to pharmaceutical companies increase, which is the main business model considered for this solution. In addition, it will open perspectives for expanding the company's portfolio, with potential for applying the technology to other types of cancer and infectious diseases. Finally, it will represent a successful case of clinical translation of a product developed entirely in Brazil, placing the country at a new level of innovation in the health area. (AU)