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CASE REPORT article

Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1472714
This article is part of the Research Topic The Growing Role of Immunotherapy and Combination Strategies in Pancreatic and Hepatobiliary Cancers View all 8 articles

PD-L1 Targeted High-Affinity Natural Killer Cell and IL-15 Superagonist N-803-Based Therapy Extends Overall Survival of Advanced Metastatic Pancreatic Cancer Patients

Provisionally accepted
Tara Seery Tara Seery 1Leonard Sender Leonard Sender 2Omid Jafari Omid Jafari 3Frank Jones Frank Jones 4Patricia Spilman Patricia Spilman 2*Sandeep B Reddy Sandeep B Reddy 2Patrick Soon-Shiong Patrick Soon-Shiong 2
  • 1 Chan Soon-Shiong Institute for Medicine, El Segundo, CA, United States
  • 2 ImmunityBio, Inc., Culver City, United States
  • 3 Medical Imaging Center of Southern California, Santa Monica, CA, United States
  • 4 NantCell, Culver City, CA, United States

The final, formatted version of the article will be published soon.

    Background. Metastatic pancreatic cancer (mPC) is an aggressive form of cancer with a poor prognosis and few therapeutic options after failure of 2 nd line treatment. Induction of immunogenic cell death (ICD) by use of relatively low dose chemo-or radiation therapy, enhancement of immune responses by the IL-15 superagonist N-803 (Anktiva®) and targeting of Programmed Death receptor Ligand 1 (PD-L1) expressing cells may offer a therapeutic approach to refractory mPC with the potential to increase overall survival (OS). Methods. From late 2019 through 2021, single-patient Investigational New Drug (spIND) protocols for five (5) mPC patients were designed and approved that generally comprised combined Abraxane (nab-paclitaxel) and gemcitabine therapy with experimental therapeutics N-803, PD-L1 targeted high-affinity natural killer (PD-L1 t-haNK) cells, and aldoxorubicin; a serum albumin binding doxorubicin pro-drug. Some patients also received stereotactic body radiation therapy (SBRT), cyclophosphamide, pembrolizumab, nivolumab and/or experimental ETBX-051 (brachyury) and/or ETBX-061 (MUC1) vaccines. Duration of spIND treatment and responses, for some patients including imaging and CA19-9 levels, and OS from initial diagnosis and from the start of spIND therapy were assessed. Findings. The line/duration of spIND therapy were, for patients one through five respectively, 2 nd line/6.4 months, 6 th line/3.5 months, 3 rd line/25.4 months, 3 rd line/7.4 months, and 4 th line/23.2 months. OS from commencement of spIND therapy was 13, 4.8, 26.9, 9 and 23.2 months; and from diagnosis 22, 21, 42, 13 and 33 months for patients one through five, respectively. Conclusions. The OS from the initiation of spIND for all patients exceeded the reported OS for the greater-than-second-line mPC patients and, for 4 of 5 patients, 2 nd line therapy. The OS of 13, 26.9, and 23.2 months for 3 patients is particularly notable. The findings here support the ongoing clinical investigations of N-803 and PD-L1 t-haNK cells in combination therapy.

    Keywords: Advanced metastatic pancreatic cancer, 3 rd line therapy, orchestrated, Multi-Modal, N-803, PD-L1 t-haNK cells, low dose chemotherapy

    Received: 29 Jul 2024; Accepted: 07 Jan 2025.

    Copyright: © 2025 Seery, Sender, Jafari, Jones, Spilman, Reddy and Soon-Shiong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Patricia Spilman, ImmunityBio, Inc., Culver City, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.