Background: Pancreatic cancer claimed 48,220 lives in the USA in 2021, with an expected median OS of 3 months after 2^nd line. We hypothesize that effective response against pancreatic cancer requires a coordinated approach that orchestrates both the innate and adaptive immune system. We further hypothesize that by inducing DAMPs to expose tumor associated antigens and orchestrating the activation of the entire immune system, we could accomplish immunogenic cell death with durable responses in this disease, previously considered immune therapy resistant. We present results of a novel combination immunotherapy protocol, the NANT Cancer Vaccine: DAMP inducing metronomic low-dose chemoradiation, cytokine-induced NK and T cell activation via N-803 (an IL-15 cytokine fusion protein), and overcoming immune evasion with off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) cell therapy infusion. Methods: We report data on 65 patients with > 2 prior lines of therapy (cohort B+C: Quilt 88), with 30 patients at 3rd line, 35 patients ≥4^th line. Patients were treated every 4 weeks with low dose DAMP inducing chemo modulating therapy including Nab-paclitaxel (100 mg/ m2 IV), Gemcitabine (600 mg/m2 IV), Aldoxorubicin HCl (150 mg/m2 IV), Cyclophosphamide (50 mg PO BID) and low-dose SBRT. This pre-conditioning therapy induces expression of tumor associated antigens including PDL1 and is followed by cytokine stimulus of endogenous NK and T cells and allogeneic off-the-shelf NK cells to initiate immunogenic cell death via the innate and adaptive system. N-803 is administered at 15 μg/kg SC and PDL-1 engineered off-the-shelf NK cells (PDL1-thaNK) are infused weekly, to induce immune memory. All treatment was conducted as outpatients. Results: Follow-up 7 days to 18 months. Median age 62, 95% ECOG 0-1. Well tolerated with mainly low grade AEs [fatigue, chills, injection site reaction ( > 50%)]. Treatment related grade ≥3 mainly associated with chemotherapy without prophylactic growth factors: anemia 46%, neutropenia 23%, thrombocytopenia 12%, all others < 10%. Patients with at least 1 Treatment related SAE = 6%; edema, pyrexia, anemia, atrial flutter. No treatment related deaths. In all patients (3^rd to 6^th line, N = 65) median OS is 5.8 months with 40% still alive; median PFS 2.3 months (95% CI: 2.0, 3.6), 32% not having progressed to date. In 3^rd line (N = 30), median OS is 6.3 months (95% CI: 5.0, 9.8). Updated data will be presented. Conclusions: Early safety and efficacy is seen in QUILT 88 of the novel immunotherapy combination of DAMP inducers, NK and T cell activation, and PDL1 t-haNK cell therapy in Pancreatic Cancer. OS in 3^rd line (6.3 months) exceeds historical results of 3 months across 19 trials (Manax ASCO GI 2019) and compares favorably with the 6.1 months in 2^nd line patients in NAPOLI-1. Clinical trial information: NCT04390399.