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.
Indication | Gene | Route of delivery | Phase | Sponsor |
Hormone Refractory Prostate Cancer | PSA VACCINE | Intratumoral | II | David M Lubaroff |
Prostate Cancer | hIL-12 | Intratumoral | Ⅲ | 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 | Ⅲ | 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 |