Abstract Ovarian cancer is the sixth most common malignancy in women and the leading cause of death from all gynecological cancers in the United States with epithelial ovarian cancer are often diagnosed with advanced- stage disease. Although clinically complete remissions are obtained in the majority of patients through a combination of cyto-reductive surgery and chemotherapy, relapse is common with 70% of patients exhibiting recurring disease and thus represents a high unmet need. Single-agent therapies used to treat the subset of patients with chemotherapy- resistant/refractory ovarian cancer include paclitaxel, PLD (peglyated liposomal doxorubicin) and topotecan. The response rate is in the 10-15% range and overall survival is approximately 12 months. Our immunotherapy is comprised of cytokine-induced NK-T cells which stealthily delivers a tumor selective vaccinia virus to the tumor microenvironment, attracted by chemokines released by the tumor and binding to tumor stress ligands. The virus is released in the tumor site and is synchronously released to kill tumor cells, reducing or eradicating the tumor. This therapeutic approach is multi-mechanistic and delivery of the oncolytic agent by the immune effector cells together may result in a durable immune response to ovarian tumor- specific antigens through a cytotoxic T-cell mechanism. The two components, vaccinia virus vvDD-CDSR and CIK cells have been tested and investigated in multiple pre-clinical and clinical studies that have demonstrated their antitumor efficacy and overall safety. In our proposed Open Phase I/II clinical study will be a dose escalation to determine a MFD/MTD. The maximum-feasible dose (MFD) will be defined as the top dose level if no MTD is defined. It is expected that a maximum of 22 patients will be required to establish the MTD for one infusion. Once an MFD/and or MTD is determined, the study moves onto Phase II part of the protocol design allowing multiple cycles up to 4, treating 6-22 patients in Arm 1 safety and 20 patients in Arm 2 efficacy. Citation Format: Pamela R. Contag. Design of a dose escalation phase 1/2 trial for a novel combined cell and oncolytic viral therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT155.