Phase 1/2, Open-label Study Evaluating Safety of Repeat Administration of Ad/PNP-F-araAMP (Ad/PNP Administered Intratumorally Followed by Intravenous Fludarabine Phosphate) in Subjects With Recurrent, Local Head and Neck Cancer

Primary Objective: The primary objective of the study is to evaluate the safety of repeat administration of a dose level of Ad/PNP plus fludarabine phosphate (F-araAMP) which demonstrated anti-tumor activity in patients with advanced head and neck cancer in a completed phase I study.
Secondary Objective: The secondary objective is to evaluate the antitumor activity of repeat administration of Ad/PNP plus F-araAMP.
FDA Office of Orphan Drugs Division is a source of funding for the overall project.

Start Date11 Feb 2019

Sponsor / Collaborator

GeoVax, Inc.

[+3]

NCT01310179 / CompletedPhase 1

Phase I, Open-label Study Evaluating the Safety of Escalating Doses of Ad/PNP-F-araAMP (Ad/PNP Administered Intratumorally With Co-administration of Fludarabine Phosphate Intravenously) in Subjects With Advanced Solid Tumors

This study will test whether it is possible to introduce new genetic material into a small portion of a tumor and have the product of the new gene not only kill those tumor cells that were infected initially, but also the surrounding tumor cells as well with limited or no harm to the patient. The desired effects of this approach are achieved by focusing potent chemotherapies directly within the tumor itself and, as a result, avoiding injury to the remainder of the body. In this study, we will use two components, the first of which is a virus, known as an adenovirus, that has been crippled (i.e., it cannot make more of itself) and loaded with a bacterial gene called E. coli purine nucleoside phosphorylase (PNP). Adenoviruses are considered to be relatively safe vehicles for gene delivery and are presently being used in numerous human trials and therapies worldwide, including a head and neck cancer therapy approved for use outside the United States. The loaded adenovirus will be used to deliver the PNP gene directly into a tumor in patients. This gene is not expected to have an effect itself. However, the gene produces PNP inside the tumor and this protein will activate the second component of the therapy, a drug called fludarabine phosphate, which is approved by the FDA for certain types of blood-cell cancers, but has not been shown to be effective against most solid tumors. The proposed therapy gives the patient several infusions of fludarabine following the injection of the virus carrying the PNP gene and, as the fludarabine enters the tumor, it will be converted by PNP into a second compound, fluoroadenine. Numerous studies in mice and rats have shown that fluoroadenine is a very potent anti-cancer agent and that it will kill the tumor cells where it is made as well as those in the immediately surrounding area.

Start Date01 Feb 2011

Sponsor / Collaborator

PNP Therapeutics, Inc.

100 Clinical Results associated with Purine nucleoside phosphorylase gene therapy(The University of Alabama)

100 Translational Medicine associated with Purine nucleoside phosphorylase gene therapy(The University of Alabama)

100 Patents (Medical) associated with Purine nucleoside phosphorylase gene therapy(The University of Alabama)

Literatures (Medical) associated with Purine nucleoside phosphorylase gene therapy(The University of Alabama)

01 Dec 2015·Journal of the Egyptian National Cancer Institute

Targeted radiotherapy potentiates the cytotoxicity of a novel anti-human DR5 monoclonal antibody and the adenovirus encoding soluble TRAIL in prostate cancer

Article

Author: Donald J. Buchsbaum ; George E. Naoum ; Tong Zhou ; Waleed Arafat

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces a death signal following binding to death receptors (DR4, DR5). We have developed a novel anti-human DR-5 monoclonal antibody (TRA-8) and adenoviral encoding TRAIL (Ad/TRAIL). Herein, we are testing the combined effect of radiotherapy and TRA-8 or Ad TRAIL in prostate cancer cells. Human prostate cancer cell lines LnCap, PC-3 and DU145 were used in this study. Cells were treated either with TRA-8 alone or Ad/TRAIL, radiation alone, or a combination of each at different doses and intervals. Cell survival using the MTS assay and colony forming assay were used to determine radiosensitization. Immunohistochemistry was used to detect bax and bcl-2. Real-time PCR was performed on mRNA of treated prostate cancer cell lines. Finally, a murine model of subcutaneous prostate cancer was used to evaluate the in vivo effect. Cell survival assays detected by MTS assay showed that prostate cell lines treated with a combination of radiation and TRA-8 showed significantly lower survival than cells treated with either radiation or TRA-8 alone. Colony forming assay and cell proliferation assays showed increased killing after combination treatment with TRA-8 or Ad/TRAIL and radiation, than either single agent alone. Mechanistic studies showed that the killing effect was due to induction of apoptosis mostly by increased expression of bax in TRA-8 or Ad/TRAIL treated cells. Additionally, RT-PCR showed an increased copy number of bax in most cells treated with TRA-8 and radiation. It is concluded that radiation and TRA-8 or Ad/TRAIL produced a synergistic effect in refractory prostrate cancer.

01 Jun 2015·Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity

Article

Author: Li Li ; Yang Yan ; Kai Liang ; Rong Li ; Songyan Li ; Yunshan Zhao ; Xiaohui Du ; Yingxin Xu ; Tingting Jia ; Huiwei Sun ; Wentao Liang

Addition of immunoregulation factor to an oncolytic adenovirus being constructed is a developmental step in tumor gene therapy; however, cytokine IL-15 has not been frequently used as a potential cancer therapy agent. Here, we constructed an E2F-1 promoter oncolytic adenovirus based on type 5 adenovirus, which induces viral replication and proliferation in targeted tumor cells. We inserted the IL-15 gene into the E3 region of the model and found that human IL-15 expressing oncolytic adenovirus (Ad-E2F/IL15) shows a more intense antitumor effect than simple oncolytic viruses (Ad-E2F) do. Precisely because IL-15 can activate natural killer (NK) cells, CD8(+)T cells, and other immune cells, in antitumor therapy, Ad-E2F/IL15 was used in combination with cytotoxic T lymphocytes (CTL) to create a virus that can induce IL-15 gene expression while lysing tumors and stimulating the activity and function of adoptive immune cells. The therapeutic effect of this therapy is clearly stronger than that of a single application of oncolytic viruses or CTL, and hence, it could be a potential new tumor therapy.

01 Nov 2014·Viral immunologyQ4 · MEDICINE

Enhancement of Ad-CRT/E7-Mediated Antitumor Effect by Preimmunization withL. lactisExpressing HPV-16 E7

Q4 · MEDICINE

Article

Author: Montes-de-Oca-Luna, Roberto ; Rojas-Martínez, Augusto ; Villatoro-Hernández, Julio ; Zavala-Flores, Laura M. ; Arce-Mendoza, Alma Y. ; Gomez-Gutierrez, Jorge G. ; Rangel-Colmenero, Blanca R. ; Saucedo-Cárdenas, Odila ; Quistián-Martínez, Deyanira ; Guzmán-López, Santos

Although current polyvalent vaccines can prevent development of cervical cancer, they cannot be used to treat patients who already have the disease. Adenovirus expressing calreticulin-E7 (Ad-CRT-E7) has shown promising results in the cervical cancer murine model. We also demonstrated that immunization with Lactococcus lactis encoding HPV-16 E7 (Ll-E7) anchored to its surface induces significant HPV-16 E7-specific immune response. Here, we assessed the combination of both approaches in the treatment of a cervical cancer animal model. Intranasal preimmunization of Ll-E7, followed by a single Ad-CRT/E7 application, induced ∼80% of tumor suppression in comparison with controls. Mice treated with a combination of Ll-E7 and Ad-CRT/E7 resulted in a 70% survival rate 300 days post-treatment, whereas 100% of the mice in the control groups died by 50 days. Significant CD8+ cytotoxic T-lymphocytes infiltration was detected in the tumors of mice treated with Ll-E7+Ad-CRT/E7. Tumors with regression showed a greater number of positive cells for in situ TUNEL staining than controls. Our results suggest that preimmunization with Ll-E7 enhances the Ad-CRT/E7-mediated antitumor effect. This treatment provides an enormous advantage over repeated applications of Ad-CRT/E7 by maintaining the effectiveness of the three-dose application of Ad-CRT/E7, but avoiding the high systemic toxicities associated with such repeat treatments.

News (Medical) associated with Purine nucleoside phosphorylase gene therapy(The University of Alabama)

25 Oct 2023

·www.biospace.com

GeoVax to Participate in Upcoming November 2023 Investor and Industry Events

ATLANTA, GA, Oct. 25, 2023 (GLOBE NEWSWIRE) -- via NewMediaWire – GeoVax Labs, Inc. (Nasdaq: GOVX), a biotechnology company developing immunotherapies and vaccines against cancers and infectious diseases, today announced that members of its senior management team and other scientific representatives will participate in four upcoming investor and industry events during November. Event details are as follows: Emerging Growth Conference, November 1-2, 2023, Virtual Date/Time: November 2, 2023 at 3:55 p.m. ET Title: GeoVax Corporate Update Speaker: David Dodd, Chairman & CEO, GeoVax Labs, Inc. For more information and to register to attend the GeoVax Presentation, please visitEmerging Growth Conference. BIO-Europe, November 6-8, 2023, Munich, Germany Senior GeoVax management will host one-on-one meetings with registered attendees. For more information, please visit Bio-Europe. If interested in meeting with management at this event, please contact the company through the conference portal, or directly at info@geovax.com. Vaccines Summit 2023, November 13-15, 2023, Boston, MA Date/Time: November 14, 2023 at 8:00 a.m. ET Session Title: MVA-vectored multi-antigen COVID-19 vaccines induce protective immunity against SARS-CoV-2 variants spanning Alpha to Omicron in preclinical animal models Speaker: Mukesh Kumar, PhD, Associate Professor, Department of Biology, Georgia State University For more information on the conference, please visitVaccines Summit 2023. World Vaccine Congress, West Coast, November 27-30, 2023, Santa Clara, CA Date/Time: November 28, 2023 at 4:20 p.m. PT Session Title: COVID-19 Vaccines for immunocompromised patients Speaker: Don Diamond, Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center Date/Time: November 30, 2023 at 1:40 p.m. PT Session Title: Design and evaluation of vaccines against hemorrhagic fevers using the MVA-VLP platform Speaker: Jason Comer, PhD, Associate Professor, Department of Microbiology and Immunology, University of Texas Medical Branch For more information on the conference, please visitWorld Vaccine Congress, West Coast. About GeoVax GeoVax Labs, Inc. is a clinical-stage biotechnology company developing novel therapies and vaccines for solid tumor cancers and many of the world’s most threatening infectious diseases. The company’s lead program in oncology is a novel oncolytic solid tumor gene-directed therapy, Gedeptin®, presently in a multicenter Phase 1/2 clinical trial for advanced head and neck cancers. GeoVax’s lead infectious disease candidate is GEO-CM04S1, a next-generation COVID-19 vaccine targeting high-risk immunocompromised patient populations. Currently in three Phase 2 clinical trials, GEO-CM04S1 is being evaluated as a primary vaccine for immunocompromised patients such as those suffering from hematologic cancers and other patient populations for whom the current authorized COVID-19 vaccines are insufficient, and as a booster vaccine in patients with chronic lymphocytic leukemia (CLL). In addition, GEO-CM04S1 is in a Phase 2 clinical trial evaluating the vaccine as a more robust, durable COVID-19 booster among healthy patients who previously received the mRNA vaccines. GeoVax has a leadership team who have driven significant value creation across multiple life science companies over the past several decades. For more information, visit our website: Company Contact: Investor Relations Contact: Media Contact: info@geovax.com paige.kelly@sternir.com sr@roberts-communications.com 678-384-7220 212-698-8699 202-779-0929

VaccinePhase 2Immunotherapy

09 May 2023

·www.biospace.com

GeoVax Labs to Participate in A.G.P.’s Virtual Healthcare Conference

ATLANTA, GA, May 09, 2023 (GLOBE NEWSWIRE) -- via NewMediaWire – GeoVax Labs Inc., (Nasdaq: GOVX), a biotechnology company developing immunotherapies and vaccines against cancers and infectious diseases, today announced that it will participate in the Alliance Global Partners’ Virtual Healthcare Conference being held May 23-24, 2023. During the event, the GeoVax management team will be conducting one-on-one investor meetings. To request a meeting with management please contact your appropriate A.G.P. representative or the conference management team at agpevents@allianceg.com. About GeoVax GeoVax Labs, Inc. is a clinical-stage biotechnology company developing novel therapies and vaccines for solid tumor cancers and many of the world’s most threatening infectious diseases. The company’s lead program in oncology is a novel oncolytic solid tumor gene-directed therapy, Gedeptin®, presently in a multicenter Phase 1/2 clinical trial for advanced head and neck cancers. GeoVax’s lead infectious disease candidate is GEO-CM04S1, a next-generation COVID-19 vaccine targeting high-risk immunocompromised patient populations. Currently in two Phase 2 clinical trials, GEO-CM04S1 is being evaluated as a COVID-19 vaccine for immunocompromised patients such as those suffering from hematologic cancers and other patient populations for whom the current authorized COVID-19 vaccines are insufficient. In addition, GEO-CM04S1 is in a Phase 2 clinical trial evaluating the vaccine as a more robust, durable COVID-19 booster among healthy patients who previously received the mRNA vaccines. GeoVax has a leadership team who have driven significant value creation across multiple life science companies over the past several decades. For more information, visit our website: . Investor Relations Contact: Rich Cockrell CG Capital 404-736-3838 govx@cg.capital

VaccinePhase 2Immunotherapy

26 Apr 2023

·www.biospace.com

GeoVax to Participate in the 4th Symposium on Infectious Diseases in the Immunocompromised Host

ATLANTA, GA, April 26, 2023 (GLOBE NEWSWIRE) -- via NewMediaWire – GeoVax Labs Inc. (Nasdaq: GOVX), a biotechnology company developing vaccines and immunotherapies against cancers and infectious diseases, today announced its participation in and sponsor support of the 4th Symposium on Infectious Diseases in the Immunocompromised Host, being held April 30 to May 2, 2023, in Seattle, Washington and hosted by the Fred Hutchinson Cancer Center. Medical leadership representation from GeoVax will attend the event and will meet and interact with the symposium speakers and attendees. The 4th Symposium on Infectious Diseases in the Immunocompromised Host brings together leaders and trainees in research and clinical care of infectious diseases in the immunocompromised host. The program features outstanding, internationally recognized experts in the field, representing more than 20 institutions, who will speak on topics including infections in solid organ transplant, hematopoietic cell transplant, and oncology. The symposium will address COVID-19, fungal disease, respiratory viruses, CMV, HHV-6, immunotherapy, the microbiome, and antimicrobial stewardship. David Dodd, GeoVax’s Chairman and CEO, commented, “We are proud to participate in this important symposium which highlights the critical need for innovative approaches to preventing and treating infections in vulnerable populations. At GeoVax, we remain committed to advancing novel vaccine technologies such as CM04S1, our next-generation COVID-19 vaccine being studied in two Phase 2 trials, that can potentially help protect and improve the lives of immunocompromised individuals, representing those who are most susceptible to infectious diseases.” About GeoVax GeoVax Labs, Inc. is a clinical-stage biotechnology company developing novel therapies and vaccines for cancers and many of the world’s most threatening infectious diseases. The company’s lead program in oncology is a novel oncolytic solid tumor gene-directed therapy, Gedeptin®, presently in a multicenter Phase 1/2 clinical trial for advanced head and neck cancers. GeoVax’s lead infectious disease candidate is GEO-CM04S1, a next-generation COVID-19 vaccine targeting high-risk immunocompromised patient populations. Currently in two Phase 2 clinical trials, GEO-CM04S1 is being evaluated as a COVID-19 vaccine for immunocompromised patients such as those suffering from hematologic cancers and other patient populations for whom the current authorized COVID-19 vaccines are insufficient. In addition, GEO-CM04S1 is in a Phase 2 clinical trial evaluating the vaccine as a more robust, durable COVID-19 booster among healthy patients who previously received the mRNA vaccines. GeoVax has a leadership team who have driven significant value creation across multiple life science companies over the past several decades. For additional information about GeoVax, visit our website: . Investor Relations Contact: Rich Cockrell CG Capital 404-736-3838 govx@cg.capital

VaccinePhase 2Immunotherapy

100 Deals associated with Purine nucleoside phosphorylase gene therapy(The University of Alabama)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Squamous Cell Carcinoma	Phase 2	US	PNP Therapeutics, Inc.	23 Feb 2019
Advanced Head and Neck Carcinoma	Phase 2	US	GeoVax Labs, Inc.	11 Feb 2019
Head and Neck Neoplasms	Phase 2	US	PNP Therapeutics, Inc.	11 Feb 2019
Recurrent Head and Neck Carcinoma	Phase 2	US	GeoVax, Inc.	11 Feb 2019
Squamous Cell Carcinoma of Head and Neck	Phase 2	-	GeoVax Labs, Inc.	-
Advanced Malignant Solid Neoplasm	Phase 1	US	PNP Therapeutics, Inc.	01 Feb 2011

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