title: Activated dendritic cells delivered in tissue compatible biomatrices induce in-situ anti-tumor CTL responses leading to tumor regression.
abstract: Dendritic cell (DC) based anti-cancer immunotherapy is well tolerated in patients with advanced cancers. However, the clinical responses seen after adoptive DC therapy have been suboptimal. Several factors including scarce DC numbers in tumors and immunosuppressive tumor microenvironments contribute to the inefficacy of DCs as cellular vaccines. Hence DC based vaccines can benefit from novel methods of cell delivery that would prevent the direct exposure of immune cells to suppressive tumor microenvironments. Here we evaluated the ability of DCs harbored in biocompatible scaffolds (referred to as biomatrix entrapped DCs; beDCs) in activating specific anti-tumor immune responses against primary and post-surgery secondary tumors. Using a preclinical cervical cancer and a melanoma model in mice, we show that single treatment of primary and post-surgery secondary tumors using beDCs resulted in significant tumor growth retardation while multiple inoculations were required to achieve a significant anti-tumor effect when DCs were given in free form. Additionally, we found that, compared to the tumor specific E6/E7 peptide vaccine, total tumor lysate induced higher expression of CD80 and CD40 on DCs that induced increased levels of IFNγ production upon interaction with host lymphocytes. Remarkably, a strong immunocyte infiltration into the host-implanted DC-scaffold was observed. Importantly, the host-implanted beDCs induced the anti-tumor immune responses in the absence of any stromal cell support, and the biomatrix structure was eventually absorbed into the surrounding host tissue. Collectively, these data indicate that the scaffold-based DC delivery may provide an efficient and safe way of delivering cell-based vaccines for treatment of primary and post-surgery secondary tumors.
authors.affiliation: Clinical Vaccine R&D Center, Chonnam National University Medical School, Gwangju, South Korea.|Department of Microbiology, Chonnam National University Medical School, Gwangju, South Korea.|Present address: GRU Cancer Center, GRU, Augusta, GA, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Verma
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
authors.forename: Jae-Tae
authors.initials: JT
authors.lastname: Lee
authors.affiliation: School of Mechanical Systems Engineering, Chonnam National University, Gwangju, South Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Min
authors.affiliation: Clinical Vaccine R&D Center, Chonnam National University Medical School, Gwangju, South Korea.|Research Center for Cancer Immunotherapy, Hwasun Hospital, Chonnam National University, Hwasun, South Korea.
authors.forename: Je Jung
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Clinical Vaccine R&D Center, Chonnam National University Medical School, Gwangju, South Korea.|Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea.
authors.forename: Shee Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Clinical Vaccine R&D Center, Chonnam National University Medical School, Gwangju, South Korea.|Department of Microbiology, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Joon Haeng
authors.initials: JH
authors.lastname: Rhee
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D059016:Tumor Microenvironment
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007166:Immunosuppressive Agents; D007371:Interferon-gamma
keywords: biomatrices; dendritic cells; immunotherapy; tumor