Delving into the Latest Updates on AR vaccine(Madison Vaccines, Inc.) with Synapse

The current protocol will examine the use of a plasmid DNA vaccine encoding AR, alone or with T-cell checkpoint blockade, to induce and/or augment therapeutic T-cells following androgen deprivation in patients with newly diagnosed prostate cancer scheduled to undergo prostatectomy. Patients without evidence of metastatic disease, with tissue remaining from a pre-treatment biopsy, and who are being considered for standard treatment by prostatectomy, will be invited to participate and will be on study for up to 15 months.

Start Date16 Dec 2021

Sponsor / Collaborator

University of Wisconsin Madison

[+3]

NCT04090528

/ Active, not recruitingPhase 2IIT

Phase II Trial of pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer

This trial will evaluate the use of one versus two DNA vaccines, delivered concurrently with PD-1 blockade using pembrolizumab followed by treatment with pembrolizumab alone, and delivered over a prolonged period of time (for a maximum of 2 years (32 cycles) or until radiographic progression) on the treatment of castrate-resistant, metastatic prostate cancer. The hypothesis to be tested is that delivering two vaccines with PD-1 blockade will elicit a greater frequency and magnitude of tumor-directed CD8+ T cells, and thereby increase the percentage of patients experiencing objective anti-tumor effect as measured by PSA declines and/or objective radiographic responses. Participants must be 18 years of age or older and can expect to be on treatment for 2 years (32 cycles) and on study for up to 7 years (including 5 years of follow up via phone).

Start Date21 Oct 2019

Sponsor / Collaborator

University of Wisconsin Madison

[+3]

NCT02411786

/ CompletedPhase 1IIT

A Phase I Study of a DNA Vaccine Encoding Androgen Receptor Ligand-Binding Domain (AR LBD), With or Without Granulocyte Macrophage Colony-Stimulating Factor Adjuvant, in Patients With Metastatic Prostate Cancer

The purpose of this study is to determine if a vaccine called pTVG-AR can enhance the participant's immune response against prostate cancer.

Start Date24 Aug 2015

Sponsor / Collaborator

University of Wisconsin Madison

[+1]

100 Clinical Results associated with AR vaccine(Madison Vaccines, Inc.)

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100 Translational Medicine associated with AR vaccine(Madison Vaccines, Inc.)

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100 Patents (Medical) associated with AR vaccine(Madison Vaccines, Inc.)

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552

Literatures (Medical) associated with AR vaccine(Madison Vaccines, Inc.)

31 Dec 2024·Drug delivery

Incompatibility of antimalarial drugs: challenges in formulating combination products for malaria

Article

Author: Mhango, Ellen K. G. ; Gizurarson, Sveinbjorn ; Sveinbjornsson, Benjamin R. ; Snorradottir, Bergthora S.

Lipophilic drugs require more advance formulation, especially if the intention is to make solutions or semisolid formulations. This also accounts for most antimalarial drugs. Although some of these antimalarial drugs are soluble in lipid vehicles, few of them, such as lumefantrine (LF), are also poorly soluble in oily vehicles. Trying to dissolve and formulate LF as a liquid formulation together with other antimalarial drugs is, therefore, a major task. When mixed in solution together with artemether (AR), precipitation occurs, sometimes with LF precipitating out on its own, and sometimes with AR precipitating out alongside LF. In this study, it was hypothesized that the use of fatty acids could lead to enhanced solubility in lipid formulation. Addition of the fatty acid solved the dissolution challenges, making LF soluble for over a year at room temperature (21-23 °C); but further research is needed to test the mechanism of action of the fatty acid. In addition, design of experiments (MODDE^® 13) revealed that the amount of fatty acid in the formulation was the only significant factor for LF precipitation.

01 May 2024·Journal of ethnopharmacology

Evaluating the toxicity of the roots of Asarum heterotropoides var. mandshuricum extracted using the decoction method: Genotoxicity, single-dose toxicity, and 13-week repeated-dose toxicity studies

Article

Author: Han, Kang-Hyun ; Back, Seng-Min ; Kim, Woojin ; Kim, Yong-Bum ; Min, Byung Sun ; Jung, Jina ; Gu, Eun-Young ; Min, Seung Eui

ETHNOPHARMACOLOGICAL RELEVANCE:

The roots of Asarum heterotropoides F. Maekawa var. mandshuricum F. Maekawa (AR) is a traditional herbal medicine used across Asia, including Korea, China, and Japan. AR exhibits a range of biological activities, such as anti-inflammatory, anti-cancer, cold treatment, and anti-nociceptive effects. Various extraction methods, including decoction, which utilizes traditional knowledge and techniques. The AR decoction extract expected to contain fewer toxicants and have reduced toxicity due to the use of hot water in the extraction process. However, scientific evidence on the toxicity of AR decoction extracts is lacking, necessitating further studies for safe usage.

AIM OF THE STUDY:

This study aimed to evaluate the genotoxicity and toxicity of single and repeated administration of AR decoction extracts.

MATERIALS AND METHODS:

The genotoxicity was assessed using a bacterial reverse mutation (Ames test), an in vitro mammalian chromosome aberration test (CA test), and an in vivo micronucleus test (MN test) in Sprague-Dawley (SD) rats. The general toxicity was evaluated through single-dose and 13-week repeated-dose toxicity studies. In the single-dose toxicity study, 40 SD rats were orally administered AR decoction extract at doses of 1000, 2000, and 5000 mg/kg. In the 13-week repeated-dose toxicity study, 140 SD rats received daily oral doses of 0, 250, 500, 1000, 2000, and 5000 mg/kg of AR decoction extract.

RESULTS:

The genotoxicity tests revealed that AR decoction extract was not genotoxic. The single-dose toxicity study showed no changes in body weight, clinical pathology, or macroscopic findings, with the approximate lethal dose (ALD) exceeding 5000 mg/kg. The 13-week repeated-dose toxicity study demonstrated no treatment-related changes in body weight, general symptoms, hematology, clinical chemistry, or urinalysis. Histopathological findings revealed hyperplasia of squamous cells in the forestomach after AR decoction extract administration, a treatment-related effect that resolved during the recovery period. The no observed adverse effect level (NOAEL) for both male and female rats was estimated to be 2000 mg/kg.

CONCLUSIONS:

This study establishes the non-toxic dose of AR decoction extract, providing a foundation for further non-clinical and clinical evaluations AR safety.

01 May 2024·Journal for ImmunoTherapy of Cancer

Sequence of androgen receptor-targeted vaccination with androgen deprivation therapy affects anti-prostate tumor efficacy

Article

Author: Gamat-Huber, Melissa ; Vakkalanka, Sita ; Muralidhar, Anusha ; McNeel, Douglas G

Rationale:

Androgen deprivation therapy (ADT) is the primary treatment for recurrent and metastatic prostate cancer. In addition to direct antitumor effects, ADT has immunomodulatory effects such as promoting T-cell infiltration and enhancing antigen processing/presentation. Previous studies in our laboratory have demonstrated that ADT also leads to increased expression of the androgen receptor (AR) and increased recognition of prostate tumor cells by AR-specific CD8+T cells. We have also demonstrated that ADT combined with a DNA vaccine encoding the AR significantly slowed tumor growth and improved the survival of prostate tumor-bearing mice. The current study aimed to investigate the impact of the timing and sequencing of ADT with vaccination on the tumor immune microenvironment in murine prostate cancer models to further increase the antitumor efficacy of vaccines.

Methods:

Male FVB mice implanted with Myc-CaP tumor cells, or male C57BL/6 mice implanted with TRAMP-C1 prostate tumor cells, were treated with a DNA vaccine encoding AR (pTVG-AR) and ADT. The sequence of administration was evaluated for its effect on tumor growth, and tumor-infiltrating immune populations were characterized.

Results:

Vaccination prior to ADT (pTVG-AR → ADT) significantly enhanced antitumor responses and survival. This was associated with increased tumor infiltration by CD4+ and CD8+ T cells, including AR-specific CD8+T cells. Depletion of CD8+T cells prior to ADT significantly worsened overall survival. Following ADT treatment, however, Gr1+ myeloid-derived suppressor cells (MDSCs) increased, and this was associated with fewer infiltrating T cells and reduced tumor growth. Inhibiting Gr1+MDSCs recruitment, either by using a CXCR2 antagonist or by cycling androgen deprivation with testosterone replacement, improved antitumor responses and overall survival.

Conclusion:

Vaccination prior to ADT significantly improved antitumor responses, mediated in part by increased infiltration of CD8+T cells following ADT. Targeting MDSC recruitment following ADT further enhanced antitumor responses. These findings suggest logical directions for future clinical trials to improve the efficacy of prostate cancer vaccines.

100 Deals associated with AR vaccine(Madison Vaccines, Inc.)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of prostate	Phase 2	United States	Bristol Myers Squibb Co.	16 Dec 2021
Adenocarcinoma of prostate	Phase 2	United States	University of Wisconsin Madison	16 Dec 2021
Adenocarcinoma of prostate	Phase 2	United States	Regeneron Pharmaceuticals, Inc.	16 Dec 2021
Prostatic Cancer	Phase 2	United States	-	10 Sep 2019
Metastatic castration-resistant prostate cancer	Phase 1	United States	Madison Vaccines, Inc.	30 Jan 2022
Metastatic Prostate Carcinoma	Phase 1	United States	University of Wisconsin Madison	24 Aug 2015

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02411786 (ESMO2019) Manual	Phase 1	Metastatic Prostate Carcinoma	40	GM-CSF+AR vaccine(Madison Vaccines, Inc.)	npyrhokfks(aadxiafgyr) = none gkxmybwdzz (invoppyfwj ) View more	Positive	30 Sep 2019