Studies have shown that both the innate and adaptive immune system are important in the immune response to neoplasms. Adaptive immunity is characterized by a highly specific response to an antigen or antigens expressed by an infectious agent or a cancer cell. The innate immune response also primes the adaptive immune response. Innate immunity is defined by a broad, non-specific, inflammatory process mediated by innate immune cells such as monocytes, natural killer cells and macrophages, and soluble mediators such as lipids and cytokines. While these definitions were based largely on the host response to infection, they can be applied to the role of the immune system in cancer. The immune system is characterized by the innate immune system and the adaptive immune system. This study reinforced the observation that locoregional therapy augments systemic therapy. Recently it was shown that hyperthermic intraperitoneal chemotherapy (HIPEC) given at the time of surgery resulted in longer recurrence free survival and overall survival when compared to surgery alone. This study showed that IP delivery of agents was a viable therapeutic option, and that IP therapy could increase efficacy of treatment. The IP regimen resulted in a 15-month increase in overall survival compared to the standard IV therapy. Patients with stage III optimally resected cancer were given cisplatin intraperitoneal (IP) and paclitaxel intravenous (IV) and IP, compared to standard IV administration of both drugs. In 2006 there was a major advance in the treatment of some women diagnosed with EOC. The presence of the bulk of disease in the peritoneal cavity, and the semi-permeable nature of the peritoneum, makes ovarian cancer an ideal candidate for the use of locoregional therapy. In most women, mortality is associated with abdominal disease. Distant metastases (lung, brain) are infrequently found, and typically occur late in the course of disease. ĭespite the aggressive nature of ovarian cancer, and its high mortality rate, the disease is largely retained to the peritoneal cavity, with metastatic seeding to all of the major organs of the peritoneal cavity. Without curative second line treatment for patients with resistant or refractory epithelial ovarian cancer (EOC), median survival is 16 months, with most of the population dying within the first 2 years. The disease course is characterized by a high rate of relapse despite an initial good response to the therapy. Standard of care for the treatment of ovarian cancer is tumor cytoreductive surgery followed by administration of platinum and taxane based chemotherapy. Ovarian cancer is the leading cause of death due to gynecological malignancies, and the fifth leading cause of death due to cancer in women. Trial Registration Identifier: NCT02948426, registered on October 28, 2016. This therapy is highly unique in that it is the first study of its type using only components of the innate immune system for the locoregional delivery consisting of autologous monocytes and dual interferons alpha and gamma. We have combined the use of autologous monocytes and interferons alpha and gamma for local–regional administration directly into the peritoneal cavity. We have developed a novel immunotherapy focused on the innate immune system for the treatment of ovarian cancer. Secondary outcome measurements of changes in the peripheral blood immune compartment and plasma cytokines will be studied for correlations of response. We have designed a standard 3 + 3 dose escalation study to explore the highest tolerated dose of interferons and monocytes infused IP in patients with chemotherapy resistant ovarian cancer. Patient monocytes are isolated through counterflow elutriation and stimulated ex vivo with interferons and infused IP through a semi-permanent catheter. Due to the highly immune suppressive properties of ovarian cancer, ex vivo stimulation of autologous patient monocytes with interferons and infusion of all three agents intraperitoneally (IP) can provide a strong pro-inflammatory environment at the site of disease to kill malignant cells. Interferons have both cytostatic and cytotoxic properties, while monocytes stimulated with interferons have potent cytotoxic properties. Locoregional immune therapy using both interferons and monocytes can be used as a novel approach. Ovarian cancer has no definitive second line therapeutic options, and largely recurs in the peritoneal cavity.
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