Development of a protocol and understanding of the mechanisms of action of the combination of Photodynamic Therapy and Immunotherapy using oligodeoxynucleotides with CpG sequences in the treatment of cervical cancer

• Grant number: 24/08873-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Biophysics - Radiology and Photobiology
• Principal Investigator: Natalia Mayumi Inada
• Grantee: Flávia Langellotti Silva
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Cervical cancer (CC) ranks fourth worldwide among the most common and deadly types of malignant neoplasms for women. Although there are several treatments available, such as hysterectomy, radiotherapy and chemotherapy, the negative impacts on the patient's life after treatment are alarming, such as loss of pregnancy capacity, sexual dysfunction and premature ovarian failure. In this context, Photodynamic Therapy (PDT) appears as a possible solution, as it consists of a non-invasive treatment approved for clinical use. From a reaction between a photosensitizer, oxygen and light, the generation of reactive oxygen species are responsible for the death of cancer cells. With such a non-aggressive approach, it is possible to preserve reproductive potential, manage outpatient management and minimize the side effects of treating patients with cervical cancer. Furthermore, to promote the complete eradication of cancer and avoid the potential risk of resurgence of the disease post-PDT, a combination with Immunotherapy, established by oligodeoxynucleotides with CpG sequences (ODN-CpG), may be advantageous. When stimulated by ODN-CpG, dendritic cells can produce IL-12, during a Th1 response pattern, which generates cell death in neoplastic cells and increases the expression of MHC class I proteins in survivors, thus recovering the visibility of the disease in the face of the defense of the body's immune system. In this project, a co-culture model between adenocarcinoma cells (HeLa -CCL-2) and dendritic cells will be tested for the effects of a combined PDT therapy with ODN-CpG, to promote an improvement in PDT in terms of eradication. complete assessment of cervical cancer. Thus, through the application of ODN-CpG class A in culture, a significant increase in the secretion of IL-12 by dendritic cells is targeted, which will act, together with PDT, as a promoter of the death of adenocarcinoma cells, and as an immunomodulatory agent, by increasing the chance that cancer cells surviving the combined therapy will be detected by the immune system and eradicated. As a result, it is expected that the therapeutic combination will be more efficient in exterminating adenocarcinoma compared to the isolated application of Photodynamic Therapy and Immunotherapy. Furthermore, the intention is to define a stimulating in vitro model of IL-12 production by dendritic cells from class A ODN-CpG. Thus, the aim is to study a new, non-invasive treatment alternative for breast cancer. cervix, protecting the woman's quality of life post-treatment and increasing the prospect of a cure.