This trial is to determine the safest dose of a triple combination (chemokine modulatory regimen or CKM) of celecoxib, interferon alfa (IFN), and rintatolimod that can be given with a DC vaccine as treatment of peritoneal surface malignancies after standard of care surgery.

The first phase of this study will determine the safest dose of IFN that can be given in combination with celecoxib and rintatolimod along with a DC vaccine. The doses of celecoxib (400 mg) and rintatolimod (200 mg) will be consistent while the dose of IFN will be increased (5, 10, or 20 MU/m2) as participants are enrolled to the trial. The high dose of IFN in combination with celecoxib and rintatolimod will be used for the next phase of the clinical trial. After surgery, participants will receive 2 cycles of the investigational treatment.

The second phase of this study will test if the investigational treatment has any effects on peritoneal surface malignancies. The doses of the combination determined in the first phase will be used in this phase of the clinical trial. After surgery, participants will receive 2 cycles of the investigational treatment, followed by standard chemotherapy as determined by their oncologist, and then 2 more cycles of the investigational treatment.

This trial will evaluate the safety and effectiveness of autologous alpha-type-1 polarized dendritic cell (alpha-DC1) vaccines (patients' autologous alpha-DC1s loaded with autologous tumor material), combined with a systemic chemokine modulation regimen [CKM; intravenous rintatolimod (TLR3 ligand, a derivative of Poly-I:C) + intravenous interferon-alfa + oral celecoxib] as adjuvant therapy, after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), in patients with peritoneal surface malignancies (PSM), including but not limited to malignant peritoneal mesothelioma and peritoneal carcinomatosis (PC) of appendiceal and colorectal origin.

All patients judged to have peritoneal surface malignancy and considered able to be cytoreduced to Peritoneal Cancer Index (PCI) Completeness of Cytoreduction (CC) score of 1 or less will undergo CRS + HIPEC. Postoperative immunotherapy will start at least 4 weeks after CRS + HIPEC.

Immunotherapy regimen will include four cycles of intranodal (3M cells) and intradermal (3M cells) αDC1 vaccines. Each booster αDC1 vaccine dose (treatment cycles 2-4) will be followed by 4-days of systemic CKM, starting the day after vaccination (IFNα [dose-escalation: 5-20 MU/m2], intravenous [IV], once a day for 4 days; rintatolimod [short-half-life TLR3 ligand] 200 mg intravenous [IV], on Wednesday and Friday only of the CKM regimen; and celecoxib 200 mg, orally, twice a day for 4 days). In order to avoid overlap between experimental immunotherapy and potential adjuvant chemotherapy (which can be clinically indicated as a part of standard care in the subset of patients), the experimental treatments will be interrupted after cycles 1 and 2, to allow adjuvant chemotherapy that is done for each patient's clinical care, and is not a part of this research study. Whenever clinically indicated as a part of standard care, adjuvant chemotherapy may start at least 5 days after completion of the 2nd cycle of immunotherapy (first booster vaccine plus the first CKM). The 3rd cycle of immunotherapy may start at least 5 days after the completion of chemotherapy.

Inclusion Criteria:

• Patients with histologically confirmed peritoneal surface malignancies, including but not limited to malignant peritoneal mesothelioma and peritoneal carcinomatosis (PC) from presumed appendiceal and colorectal primary tumors. Most patients will have received extensive prior treatments, due to the recurrent nature of PC. Prior therapies involve previous CRS, local and systemic chemotherapies. None of these prior treatments disqualifies the patient from receiving the protocol-mandated experimental treatment.
• Patients must be deemed able to undergo optimal cytoreductive surgery (CRS) defined as CC-score of 0 or 1 based on imaging.

Cytoreduction is defined as the burden of residual disease nodules left at the end of surgery (CC-0: no visible disease; CC-1: residual tumor nodules ≤ 2.5 mm in size; CC-2: residual tumor nodules 2.5 mm - 2.5 cm in size; CC-3: residual tumor nodules > 2.5 cm in size).

• Patients may be enrolled in the study regardless of prior chemotherapy regimens
• An ECOG performance status of 0, 1 or 2
• Age equal to 18 years or older
• Patients must be able to understand and be willing to sign a written informed consent document
• Able to swallow pills
• Must have normal organ and marrow function as defined below:

Platelet ≥ 75,000/µL Hemoglobin ≥ 9.0 g/dL Hematocrit ≥ 27.0% Absolute Neutrophil Count (ANC) ≥ 1500/µL WBC >2000/mm3 Creatinine < 1.5 x institutional upper limit of normal (ULN), OR Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels greater than 1.5 x ULN Total bilirubin ≤ 1.5 x ULN AST(SGOT) and ALT(SGPT) ≤ 2.5 X ULN

• Must be eligible for pheresis within 8 weeks of surgery
• Availability of sufficient number of tumor cells for cryopreservation and subsequent vaccine production
• Must have had HIPEC during surgery
• Must have a CC score of 0

Exclusion Criteria:

• Infection of tumor tissue with pathogens resistant to radiation and fungizone
• Patients on systemic immunosuppressive agents, including steroids. Patients who are able to be removed from immunosuppressives at least 5 days prior to the first vaccine will be considered eligible.
• Patients with active autoimmune disease or history of transplantation. Patients with indolent or chronic autoimmune disease not requiring steroid treatment are considered eligible.
• Patients who are pregnant or nursing
• Patients experiencing a cardiac events (acute coronary syndrome, myocardial infarction, or ischemia) within the 3 months prior to accrual
• Patients with a New York Heart Association classification of III or IV
• Prior allergic reaction or hypersensitivity to celecoxib or NSAIDs