O-035 Ex vivo photodynamic therapy approach using a nanovesicular photosensitizer to allow safe autotransplantation of ovarian tissue from leukemia patients

Abstract

Abstract Study question Is it possible to purge leukemia cells from ovarian tissue (OT) fragments before transplantation? Summary answer Our photodynamic therapy (PDT) approach showed to efficiently destroy leukemia cells from a tumor model, indicating the feasibility of this technique to purge OT samples. What is known already Autotransplantation of the cryopreserved OT is the most suitable option to preserve fertility for prepubertal girls and women that require immediate cancer treatment [1, 2]. Up to now, more than 200 live births have already been reported after OT cryopreservation and transplantation [3]. Leukemia is the 12th most common cancer in Europe among prepubertal girls and women of reproductive age [4]. Unfortunately, once their health has been restored, autotransplantation of cryopreserved OT for leukemia patients is not advised due to the high risk of transferring malignant cells back to the patient, leading to leukemia recurrence [3]. Study design, size, duration To safely transplant the OT from these patients and restore their fertility, our goal here was to develop a PDT strategy to eliminate leukemia ex vivo. To this end, we designed OR141-loaded niosomes (ORN) to create the most effective formulation for ex vivo purging OT fragments from myelogenous leukemia cells. Participants/materials, setting, methods After establishing the best ORN formulation, our PDT approach was used to eradicate HL60 from ex vivo tumor models prepared by microinjection of cancer cell suspension in ovarian fragments [5]. Additionally, we evaluated the effect of ORN-based PDT on follicle density, survival, and tissue quality was evaluated after 7-day xenotransplantation to SCID mice. Main results and the role of chance The ex vivo purging of tumor models demonstrated that the PDT strategy with ORN could selectively eradicate the malignant cells from tissue fragments without affecting ovarian tissue normal cells, as evidenced by PCR and immunohistochemical analysis. Regarding the effect of our PDT approach on follicle population and OT quality, our results after xenotransplantation revealed no significant difference between the follicle density of control (non-treated, grafted OT) and ORN-treated groups (2.38 ± 0.63 and 3.21 ± 1.94 morphologically normal follicles/mm2, respectively). In addition, the results showed that the control and ORN-treated ovarian tissue can be equally vascularized (7.65±1.45% and 9.89±2.21%, respectively). Moreover, the proportion of fibrotic area in control and ORN-treated groups were 15.96±5.94%, and 13.32±3.05%, which is not significantly different from the pre-graft fragments (14.22±6.65%). Limitations, reasons for caution This study did not use OT fragments from leukemia patients, but tumor models created after injection of HL60 cells in OT from healthy patients. Therefore, while the results are promising, it still remains to assess if our PDT approach will be equally successful to eliminate malignant cells from leukemia patients. Wider implications of the findings Our results showed that the purging procedure causes no significant impairing effect on follicles development and tissue quality, suggesting our novel PDT procedure could be a promising strategy to destroy leukemia cells in fragments of ovarian tissue allowing its safe transplantation in cancer survivors. Trial registration number not applicable