Table 1.
Human Gene Therapy Protocols for Prostate Cancer*
| Strategy | Gene | Vector | Title |
|---|---|---|---|
| Immunotherapy | GM-CSF | Retrovirus | Phase I/II study of autologous human GM-CSF gene-transduced |
| prostate cancer vaccines in patients with metastatic | |||
| prostate carcinoma | |||
| Immunotherapy | IL-2/ | Retrovirus | Phase I/II study of immunization with MHC class I matched |
| Interferon- γ | allogeneic human prostatic carcinoma cells engineered to | ||
| secrete IL-2 and interferon-γ | |||
| Antisense | c-myc | Retrovirus | Gene therapy for the treatment of advanced prostate cancer by |
| (gene replacement) | in vivo transduction with prostate-targeted retroviral vectors | ||
| expressing antisense c-myc RNA | |||
| Immunotherapy | PSA promoter | Vaccinia | Phase I study of recombinant vaccinia that expresses PSA in adult |
| patients with adenocarcinoma of the prostate | |||
| Immunotherapy | IL-2 | Liposome | Phase I study of autologous human IL-2 gene-modified tumor |
| cells in patients with locally advanced or metastatic | |||
| prostate cancer | |||
| Suicide gene | Thymidine | Adenovirus | Phase I study of adenoviral vector delivery of the HSV-tk gene |
| (cytoreductive) | kinase | and the intravenous administration of ganciclovir in men with | |
| local recurrence of prostate cancer after radiation therapy | |||
| Immunotherapy | PSA promoter | Vaccinia | Phase I trial of recombinant vaccinia virus that expresses PSA in |
| patients with adenocarcinoma of the prostate | |||
| Immunotherapy | PSA promoter | Vaccinia | Phase I/II clinical trial evaluating the safety and biologic activity |
| of recombinant vaccinia-PSA vaccine in patients with serologic | |||
| recurrence of prostate cancer following radical prostatectomy | |||
| Immunotherapy | IL-2 | Liposome | Phase I study evaluating the safety and efficacy of IL-2 gene |
| therapy delivered by lipid-mediated gene transfer (leuvectin) in | |||
| prostate cancer patients | |||
| Suicide gene | Thymidine | Adenovirus | Phase I trial of adenoviral-mediated HSV-tk gene transduction in |
| (cytoreductive) | kinase | conjunction with ganciclovir therapy as neoadjuvant treatment | |
| for patients with clinically localized (stage T1c and T2b&c) | |||
| prostate cancer prior to radical prostatectomy | |||
| Gene replacement | p53 | Adenovirus | Phase I study in patients with locally advanced or recurrent |
| adenocarcinoma of the prostate using SCH58500 (rAd/p53) | |||
| administered by intratumoral injection | |||
| Immunotherapy | GM-CSF | Retrovirus | Phase I/II study of allogeneic human GM-CSF gene-transduced |
| irradiated prostate cancer cell vaccines in patients with | |||
| prostate cancer | |||
| Principal Investigators | Institution | Status | FDA Protocol ID No. |
| J. Simons | Johns Hopkins Oncology Center, | Open | 9408-082 |
| Baltimore | |||
| B. Gansbacher | Memorial Sloan-Kettering Cancer | Open | 9503-102 |
| Center, New York | |||
| M. Steiner, J. Holt | Vanderbilt University Medical Center, | Open | 9509-123 |
| Nashville, Tenn | |||
| A. Chen | National Naval Medical Center, | Open | 9509-126 |
| Bethesda, Md | |||
| D. Paulson, K. Lyerly | Duke University Medical Center, | Open | 9510-132 |
| Durham, NC | |||
| P. Scardino, T. Thompson, | Baylor College of Medicine, | Open | 9601-44 |
| S. Woo | Houston | ||
| D. Kufe, J. Eder | Dana Farber Cancer Institute, | Open | 9609-160 |
| Boston | |||
| M. Sanda | University of Michigan Urology Clinics, | Open | 9702-176 |
| Ann Arbor | |||
| A. Belldegrun | UCLA School of Medicine, | Open | 9703-184 |
| Los Angeles | |||
| S. Hall, S. Woo | Mount Sinai School of Medicine, | Open | 9705-187 |
| New York | |||
| A. Belldegrun, R. Figlin | UCLA School of Medicine, | Open | 9706-192 |
| Los Angeles | |||
| J. Simons | Johns Hopkins Oncology Center, | Open | 9708-205 |
| Baltimore | |||
| Strategy | Gene | Vector | Title |
| Gene replacement | p53 | Adenovirus | Tolerance and efficacy study of intraprostatic INGN 201 followed |
| by pathologic staging and possible radical prostatectomy in | |||
| patients with locally advanced prostate cancer | |||
| Suicide gene | Thymidine | Adenovirus | Neoadjuvant preradical prostatectomy gene therapy (HSV-tk gene |
| (cytoreductive) | kinase | transduction followed by ganciclovir) in patients with poor | |
| prognostic indicators | |||
| Oncolytic virus | PSA promoter | Adenovirus | Phase I study of the intraprostatic injections of CN706, a PSA |
| (cytoreductive) | gene-regulated cytolytic adenovirus, in patients with locally | ||
| recurrent cancer following definitive radiotherapy | |||
| Immunotherapy | MUC-1/IL-2 | Vaccinia | Phase I/II trial of antigen-specific immunotherapy in MUC-1-positive |
| patients with adenocarcinoma of the prostate using | |||
| vaccinia virus-MUC1 -IL-2 (TG 1031) | |||
| Suicide gene | Thymidine | Adenovirus | Phase I study of Ad-OC-tk plus valacyclovir for the treatment |
| (cytoreductive) | kinase | of metastatic or recurrent prostate cancer | |
| Immunotherapy | PSA promoter | Vaccinia/ | Phase II randomized trial of recombinant fowlpox and |
| fowlpox | recombinant vaccinia virus-expressing PSA in patients with | ||
| adenocarcinoma of the prostate | |||
| Immunotherapy | GM-CSF | Retrovirus | Phase I/II study of a prime-boost schedule of human GM-CSF |
| gene-transduced irradiated prostate allogeneic cancer cell vaccines | |||
| (allogeneic prostate GVAX) in hormone-naive prostate cancer | |||
| patients | |||
| Immunotherapy | PSA promoter | Vaccinia/ | Phase II randomized study of vaccine treatment of advanced |
| fowlpox | prostate cancer | ||
| Immunotherapy | PSA | Safety and feasibility study of active immunotherapy in patients | |
| with metastatic prostatic carcinoma using autologous dendritic | |||
| cells pulsed with RNA-encoding PSA | |||
| Immunotherapy | IL-2 | Liposome | Phase II study evaluating the safety and efficacy of neoadjuvant |
| leuvectin immunotherapy for the treatment of prostate cancer | |||
| Suicide gene | Thymidine | Adenovirus | Phase I/II study evaluating HSV-tk + valacyclovir gene therapy |
| (cytoreductive) | kinase | in combination with radiotherapy for prostate cancer | |
| Principal Investigators | Institution | Status | FDA Protocol ID No. |
| C. Logothetis | University of Texas M. D. Anderson | Open | 9710-217 |
| Cancer Center, Houston | |||
| D. Kadmon, | Baylor College of Medicine, | Open | 9801-229 |
| E. Aguilar-Cordova | Houston | ||
| J. Simons | Johns Hopkins School of Medicine, | Open | 9802-236 |
| Baltimore | |||
| R. Figlin | UCLA School of Medicine, | Open | 9805-251 |
| Los Angeles | |||
| T. Gardner, L. Chung | University of Virginia Health Sciences Center, | Open | 9812-276 |
| Charlottesville | |||
| J. Eder | Dana Farber Cancer Institute, | Under review | 9901-282 |
| Boston | |||
| E. Small | University of California, | Open | 9901-283 |
| San Francisco | |||
| H. Kaufman | Albert Einstein College of Medicine, | Under review | 9902-293 |
| Bronx, NY | |||
| J. Vieweg | Duke University Medical Center, | Open | 9904-306 |
| Durham, NC | |||
| A. Belldegrun | UCLA School of Medicine, | Under review | 9905-312 |
| Los Angeles | |||
| B. Butler, E. Aguilar-Cordova | Baylor College of Medicine, Houston | Open | 9906-324 |
| Houston |
GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-2, interleukin-2; MHC, major histocompatability complex; HSV-tk, herpes simplex virus thymidine kinase; PSA, prostate-specific antigen; BRCA1, breast cancer susceptibility gene 1.
*
As of 9/22/99.