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 ; Angarita, Fernando A ; Mealiea, David ; 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 ; Breitbach, Caroline J ; McCart, J Andrea ; Wieckowski, Eva ; Hu, Kang ; O'Malley, Mark E ; Rao, Uma N M ; 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.

Oncolytic Virotherapy

<p>A cautionary note on the selectivity of oncolytic poxviruses</p>

Article

Author: Tang, Bingtao ; Roy, Edward J ; McFadden, Grant ; Liu, Jia ; Bartlett, David L ; Guo, Zong Sheng ; Shisler, Joanna L

BACKGROUNDOncolytic viruses selectively infect cancer cells while avoiding infection of normal cells. Usually, selectivity is demonstrated by injecting a virus into tumor-bearing mice and observing infection and lysis of tumor cells without infection of other tissues. The general view is that this selectivity is due to tropisms of the virus. However, apparent selectivity could be due to accessibility. For example, intravenously injected virus may not gain access to cells within the central nervous system (CNS) because of the blood-brain barrier.PURPOSEWe tested the CNS safety of two oncolytic poxviruses that have been demonstrated to be safe for treatment of peripheral tumors (vaccinia virus vvDD-IL15-Rα and myxoma virus vMyx-IL15Rα-tdTr).METHODSTwo poxviruses were tested for selectivity in vitro and in vivo.RESULTSBoth viruses infected glioma cells in vitro. In vivo, both viruses infected glioma cells and did not infect neurons when injected into a tumor or into the normal striatum. However, viral gene expression was observed in ependymal cells lining the ventricles, implying that these poxviruses were not as selective as originally predicted. For vvDD-IL15-Rα, some tumor-bearing mice died soon after virus treatment. If the same titer of vvDD-IL15-Rα was injected directly into the lateral cerebral ventricle of nontumor-bearing mice, it was uniformly fatal. Infection of ependymal cells, subventricular cells, and meninges was widespread. On the other hand, vMyx-IL15Rα-tdTr only transiently infected ependymal cells and was safe even when injected directly into the lateral cerebral ventricles. The two poxviruses also differed in their infection of dendritic cells; vvDD-IL15-Rα infected dendritic cells and lysed them but vMyx-IL15Rα-tdTr did not.CONCLUSIONVaccinia virus vvDD-IL15-Rα is very promising for treating cancer types outside of the brain. However, for cancers located within the brain, myxoma virus vMyx-IL15Rα-tdTr offers a safer alternative.

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

R&D Status

10 top R&D records.

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

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