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Adenovirus has been proved as an excellent gene therapy vector. To date, more than 535 clinical trials have been carried out using adenovirus vectors for gene delivery [7], and promising gene therapy outcomes from recombinant adenovirus have been achieved from clinical trials for a great number of diseases (Table 1), especially for cancer treatment. Gene delivery by adenovirus is to “correct” and rebuild broken down system or infected tissues in vivo, and this kind of gene therapy has been used as an alternative in clinical trials today and proved to be effective in treatment of several cancers, including Prostate Cancer [8], Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) [9], Non-small Cell Lung Cancer (NSCLC) [10], Melanoma [11], Renal cell carcinoma [12]. Among them, multimodal oncolytic adenoviruses have been used as biological therapeutics to promote tumor elimination in prostate cancer patients; adenovirus encoding chimeric CD154 (Ad-ISF35) can enhance the ability of CSL cells to function as antigen-presenting cells and increase their sensitivity to clearance based on immune-effector mechanisms; a large number of adenovirus-encoded transgenes (IL-1, GM-CSF, CD40L, IL-12, mda-7/IL24, IFN-gamma) vaccination could activate the immune system and induce cell death in an immunogenic fashion.

Table1. Selected clinical trials using adenovirus vectors.
Indication Gene Route of delivery Phase Sponsor
Hormone Refractory Prostate Cancer PSA VACCINE Intratumoral II David M Lubaroff
Prostate Cancer hIL-12 Intratumoral Baylor College of Medicine
Localized Prostate Cancer REIC/Dkk3 Intratumoral I–II Momotaro-Gene Inc.
Castration-resistant Prostate Cancer DCVac/PCa subcutaneously I–II Sotio a.s.
Recurrent Prostate Cancer hIL-12 Intratumoral I Simon Hall
PSA VACCINE Intratumoral David M Lubaroff
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) ISF35 Intranodal I University of California, San Diego
ISF35 Intranodal II Januario Castro, M.D.
CD19CAR Intravenous I Baylor College of Medicine
Non-small Cell Lung Cancer yCD/mutTKSR39rep-ADP intratumoral I Benjamin Movsas, M.D.
CCL21 vaccine intratumoral I VA Office of Research and Development
MAGEA3 intratumoral I–II Turnstone Biologics, Inc.
CCL21 vaccine intratumoral I Jonsson Comprehensive Cancer Center
Melanoma CCL21 vaccine intradermal I H. Lee Moffitt Cancer Center and Research Institute
RSV-TK intratumoral I National Human Genome Research Institute (NHGRI)
Renal cell carcinoma DC vaccine subcutaneously I–II Affiliated Hospital to Academy of Military Medical Sciences


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