{
  "abstract": "Background To date, no radioimmunotherapy (RIT) regimen has been approved by US Food and Drug Administration for the treatment of pancreatic cancers. Highly desmoplastic and immune-desert phenotypes of pancreatic cancer remain two major hurdles that attenuate the efficacy of conventional treatment (radiotherapy and chemotherapy) and immunotherapeutic (immune checkpoint inhibitors and chimeric antigen receptor T cells).Method To overcome these hurdles, an oncolytic adenovirus (oAd) co-expressing interleukin-12, granulocyte macrophage colony-stimulating factor, and relaxin (HY-oAd) was investigated in combination with programmed death-ligand 1 (PD-L1)-targeted RIT (lutetium-177-labeled atezolizumab ( 177Lu-aPD-L1)).Results HY-oAd treatment was shown to elevate PD-L1 expression level and promoted degradation of extracellular matrix of pancreatic tumors, resulting in increased aPD-L1 or 64Cu-aPD-L1 accumulation in tumor tissues. HY-oAd in combination with either aPD-L1 or 177Lu-aPD-L1 (HY-oAd+aPD-L1 or HY-oAd+177Lu-aPD-L1, respectively) elicited more potent antitumor effect against the pancreatic tumors than respective monotherapy in both subcutaneous and orthotopic pancreatic tumor models. The potent antitumor effect of HY-oAd+aPD-L1 combination therapy was due to superior intratumoral infiltration and activation of dendritic cells and CD4+ or CD8+ T cells over the respective monotherapy.Conclusion Collectively, our findings demonstrate that HY-oAd can enhance intratumoral accumulation of 177Lu-aPD-L1 in a multifaceted manner to elicit synergistic antitumor immune response against desmoplastic and poorly immunogenic pancreatic tumors.",
  "authors": [
    {
      "affiliations": [
        "Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea",
        "Institute of Nano Science and Technology (INST), Seoul, Republic of Korea",
        "Hanyang Institute of Bioscience and Biotechnology (HY-IBB), Hanyang University, Seoul, Republic of Korea"
      ],
      "name": "A-Rum Yoon"
    },
    {
      "affiliations": [
        "Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea",
        "Radiological and Medical Sciences, University of Science and Technology (UST), Seoul, Republic of Korea"
      ],
      "name": "Seungyoun Kim"
    },
    {
      "affiliations": [
        "Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea"
      ],
      "name": "Ji Yi"
    },
    {
      "affiliations": [
        "Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea",
        "Radiological and Medical Sciences, University of Science and Technology (UST), Seoul, Republic of Korea"
      ],
      "name": "Javeria Zaheer"
    },
    {
      "affiliations": [
        "Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea"
      ],
      "name": "Hyeongi Kim"
    },
    {
      "affiliations": [
        "Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea"
      ],
      "name": "Je Hyeon Seo"
    },
    {
      "affiliations": [
        "GeneMedicine Co., Ltd., 222 Wangsimni-ro, Seoul, Republic of Korea"
      ],
      "name": "Jinwoo Hong"
    },
    {
      "affiliations": [
        "Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea"
      ],
      "name": "Jeongwon Lee"
    },
    {
      "affiliations": [
        "Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea"
      ],
      "name": "Hyeju Jeong"
    },
    {
      "affiliations": [
        "Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea",
        "Radiological and Medical Sciences, University of Science and Technology (UST), Seoul, Republic of Korea"
      ],
      "name": "Joycie Shanmugiah"
    },
    {
      "affiliations": [
        "Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea"
      ],
      "name": "Ju Hee Kim"
    },
    {
      "affiliations": [
        "Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea",
        "Institute of Nano Science and Technology (INST), Seoul, Republic of Korea",
        "Hanyang Institute of Bioscience and Biotechnology (HY-IBB), Hanyang University, Seoul, Republic of Korea"
      ],
      "name": "In-Wook Kim"
    },
    {
      "affiliations": [
        "Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea",
        "Radiological and Medical Sciences, University of Science and Technology (UST), Seoul, Republic of Korea"
      ],
      "name": "Jin Su Kim"
    },
    {
      "affiliations": [
        "Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea",
        "Institute of Nano Science and Technology (INST), Seoul, Republic of Korea",
        "Hanyang Institute of Bioscience and Biotechnology (HY-IBB), Hanyang University, Seoul, Republic of Korea",
        "GeneMedicine Co., Ltd., 222 Wangsimni-ro, Seoul, Republic of Korea"
      ],
      "name": "Chae-Ok Yun"
    }
  ],
  "title": "Oncolytic adenovirus in combination with PD-L1-targeted radioimmunotherapy exerts synergistic antitumor effect against pancreatic cancer",
  "uid": "e31a7d62-3192-507e-839e-ab6028e19357"
}