This trial proposes to evaluate the immunologic and potential clinical effectiveness of intensive locoregional sequential intraperitoneal (IP) cisplatin (IPC) with intravenous (iv) paclitaxel followed by peritoneal infusion of a chemokine modulatory (CKM) regimen composed of a cocktail of IP rintatolimod and interferon-alpha (IFNα) for patients with advanced stage ovarian cancer (III-IV) in the primary neoadjuvant setting. It was previously determined the tolerable dose of IPC-CKM. This study will add intradermal (ID) autologous αDC1 vaccines (known to be nontoxic) to the tolerable IPC-CKM regimen and systemic Keytruda (pembrolizumab). To optimize the pattern of immunity, all patients will also receive oral celecoxib (COX2 inhibitor).

In addition to its typically late detection, the difficulty in treating OvCa results from its particular adeptness at avoiding immune elimination. Several vaccine trials targeting ovarian cancer have recently reported a lack of efficacy with vaccine only approaches. OvCa cells have been reported to display numerous defects in their MHC class I antigen-presenting capacity, involving loss of HLA alleles and loss of the molecules involved in the generation of antigenic peptides. In addition to these passive mechanisms of immune subversion, OvCa employs a series of active suppressive mechanisms, involving the suppression of endogenous immune cells and innate immune response pathways, and a particularly high ability to attract regulatory T cells (Tregs), mediated by elevated expression of CXCL12 and CCL22 2. It is suspected that massive chemotherapy-induced apoptosis may further promote this modulation by enhancing local immunity. These considerations suggest that effective immunotherapies of OvCa may need to involve countermeasures to both these modes (passive and active) of immune subversion. Since αDC1-induced CD8+ T cells express particularly high levels of the typical CTL-associated chemokine receptors (CXCR3 and CCR5), the therapeutic benefit of αDC1 vaccination is likely to be enhanced by the CKM therapies, able of selectively enhancing CXCL10 (and other CXCR3 ligands) as well as CCR5 ligands, such as CCL5/RANTES, in order to promote the entry of the vaccination-induced effector cells to tumor tissue.

Inclusion Criteria:

1. Patients must have advanced stage (III-IV) epithelial carcinoma or carcinosarcoma of ovarian, tubal or peritoneal origin.

   a. Histologic documentation of the original primary tumor is required via a pathology report.

2. Patients must be eligible for cancer-related definitive therapy with neoadjuvant chemotherapy.

3. Patients must be chemo-naive and receiving therapy in primary first-line neoadjuvant setting.

4. Patients must have ECOG performance of 0-1.

5. Patients must be reasonable candidate for interval debulking surgery as well as for IP platinum-based combination chemotherapy regimen, with no prior evidence of clinically significant intra-abdominal adhesions, persistent abdominal wall infections, renal disease or bowel obstruction.

6. At least one lesion must be considered to be large enough for biopsy and resection to yield greater than 2 grams of tumor for tumor loading of αDC1's and immunoassays at the discretion of the treating investigator and/or surgeon.

7. Patients must have measurable disease per iRECIST criteria.

8. Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception prior to study entry, during the course of the study, and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.

9. Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met:

   a. Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.

10. Patients must be willing to undergo leukapheresis.

11. Patients must be willing to adhere to protocol requirements.

12. Patients must have adequate:

    1. Bone marrow function:

       • Absolute neutrophil count (ANC) greater than or equal to 1,500/μL
       • Platelets greater than or equal to 100,000/μL
       • Hemoglobin greater than or equal to 8.0 g/dL

    2. Renal function:

       - Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)

    3. Hepatic function:

       • Bilirubin less than or equal to 1.5 x ULN
       • SGOT and alkaline phosphatase less than or equal to 2.5 x ULN

13. Patients who have signed informed consent and authorization permitting release of personal health information.

14. Patients must be ≥ 18 years of age.

15. Patient must be able to swallow oral medication and have no absorption related medical concern as deemed by the investigator.

Exclusion Criteria:

1. Patients with sarcoma.

2. Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis).

3. Patients with a known allergy to cisplatin or taxane chemotherapy. Patients with carboplatin allergy may be included if they tolerate a test dose of IV cisplatin given in monitored floor conditions. Patients who are allergic to paclitaxel can be alternatively treated with abraxane.

4. Patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH), or systemic corticosteroids.

   a. Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained.

5. Patients with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; patients who have acquired, hereditary, or congenital immunodeficiencies.

6. Patients with uncontrolled diseases other than cancer will be excluded.

7. Patients who have contraindications to the use of NSAID's like chronic renal failure, coronary artery disease, or bleeding ulcers.

8. Patients who have contraindications to the use of interferon α-2b (Bioferon), including hypersensitivity to interferon-α or any component of the product, autoimmune hepatitis, and decompensated liver disease.

9. Patients with tumors of low malignant potential, except ovarian pseudomyxoma or with no peritoneal disease.

10. Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.

11. Patients with previous pelvic radiation therapy.