EGFR modulators(Epidermal growth factor receptor erbB1 modulators), SSTR modulators(Somatostatin receptor modulators), FCY1 modulators(Cytosine deaminase modulators)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Breast CancerColorectal CancerLiver Cancer+ [3]

Inactive Indication-

Originator Organization

SillaJen, Inc.

Active Organization

SillaJen, Inc.University of Pittsburgh Medical Center

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

100 Clinical Results associated with Double-deleted Vaccinia Virus Plus CD/ SMR(SillaJen)

100 Translational Medicine associated with Double-deleted Vaccinia Virus Plus CD/ SMR(SillaJen)

100 Patents (Medical) associated with Double-deleted Vaccinia Virus Plus CD/ SMR(SillaJen)

Literatures (Medical) associated with Double-deleted Vaccinia Virus Plus CD/ SMR(SillaJen)

01 Jun 2023·Molecular Therapy - Oncolytics

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis

Article

Author: Sellers, Clara ; Mealiea, David ; Angarita, Fernando A ; Ottolino-Perry, Kathryn ; Ginj, Mihaela ; Acuna, Sergio A ; Okamoto, Lili ; Scollard, Deborah ; Reilly, Raymond ; McCart, J Andrea

Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy. We hypothesized that vvDD-SSTR combined with a radiolabeled somatostatin analog could be deployed as radiovirotherapy in a colorectal cancer peritoneal carcinomatosis model, producing tumor-specific radiopeptide accumulation. Following vvDD-SSTR and ¹⁷⁷Lu-DOTATOC treatment, viral replication and cytotoxicity, as well as biodistribution, tumor uptake, and survival, were evaluated. Radiovirotherapy did not alter virus replication or biodistribution, but synergistically improved vvDD-SSTR-induced cell killing in a receptor-dependent manner and significantly increased the tumor-specific accumulation and tumor-to-blood ratio of ¹⁷⁷Lu-DOTATOC, making tumors imageable by microSPECT/CT and causing no significant toxicity. ¹⁷⁷Lu-DOTATOC significantly improved survival over virus alone when combined with vvDD-SSTR but not control virus. We have therefore demonstrated that vvDD-SSTR can convert receptor-negative tumors into receptor-positive tumors and facilitate molecular imaging and PRRT using radiolabeled somatostatin analogs. Radiovirotherapy represents a promising treatment strategy with potential applications in a wide range of cancers.

01 Jan 2015·Molecular TherapyQ1 · MEDICINE

First-in-man Study of Western Reserve Strain Oncolytic Vaccinia Virus: Safety, Systemic Spread, and Antitumor Activity

Q1 · MEDICINE

Article

Author: Zeh, Herbert J ; Ramalingam, Lekshmi ; Moon, Anne ; Downs-Canner, Stephanie ; Daneshmand, Manijeh ; Guo, Zong Sheng ; Bartlett, David L ; Thorne, Stephen H ; Jones, Heather L ; Kalinski, Pawel ; Bell, John C ; Hwang, Tae-Ho ; McCart, J Andrea ; O'Malley, Mark E ; Hu, Kang ; Rao, Uma N M ; Wieckowski, Eva ; Breitbach, Caroline J ; Kirn, David H

Oncolytic viral therapy utilizes a tumor-selective replicating virus which preferentially infects and destroys cancer cells and triggers antitumor immunity. The Western Reserve strain of vaccinia virus (VV) is the most virulent strain of VV in animal models and has been engineered for tumor selectivity through two targeted gene deletions (vvDD). We performed the first-in-human phase 1, intratumoral dose escalation clinical trial of vvDD in 16 patients with advanced solid tumors. In addition to safety, we evaluated signs of vvDD replication and spread to distant tumors, pharmacokinetics and pharmacodynamics, clinical and immune responses to vvDD. Dose escalation proceeded without dose-limiting toxicities to a maximum feasible dose of 3 × 10(9) pfu. vvDD replication in tumors was reproducible. vvDD genomes and/or infectious particles were recovered from injected (n = 5 patients) and noninjected (n = 2 patients) tumors. At the two highest doses, vvDD genomes were detected acutely in blood in all patients while delayed re-emergence of vvDD genomes in blood was detected in two patients. Fifteen of 16 patients exhibited late symptoms, consistent with ongoing vvDD replication. In summary, intratumoral injection of the oncolytic vaccinia vvDD was well-tolerated in patients and resulted in selective infection of injected and noninjected tumors and antitumor activity.

Cancers

Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models

Article

Author: Bartlett, David L ; Zhao, Jinshun ; Ren, Jinghua ; Chen, Lingjuan ; Ye, Junjie ; Waltermire, Julia ; Guo, Zongsheng ; Liu, Zuqiang

The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4+ and CD8+ T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy.

100 Deals associated with Double-deleted Vaccinia Virus Plus CD/ SMR(SillaJen)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 1	-	SillaJen, Inc.	-
Breast Cancer	Phase 1	-	University of Pittsburgh Medical Center	-
Liver Cancer	Phase 1	-	SillaJen, Inc.	-
Liver Cancer	Phase 1	-	University of Pittsburgh Medical Center	-
Melanoma	Phase 1	-	SillaJen, Inc.	-
Melanoma	Phase 1	-	University of Pittsburgh Medical Center	-
Pancreatic Cancer	Phase 1	-	SillaJen, Inc.	-
Pancreatic Cancer	Phase 1	-	University of Pittsburgh Medical Center	-
Squamous Cell Carcinoma of Head and Neck	Phase 1	-	University of Pittsburgh Medical Center	-
Squamous Cell Carcinoma of Head and Neck	Phase 1	-	SillaJen, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Double-deleted Vaccinia Virus Plus CD/ SMR(SillaJen)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation