Sillajen begins phase iii trial of pexavec for colon. A phase iii study of pexavec oncolytic virus in combination with. Pexa vec is a groundbreaking oncolytic product with significant potential in the treatment of hcc, and we are excited to apply our 20 years of expertise in virus manufacturing to help bring this. Jun 12, 2018 the trial was run in partnership with transgene, a french biotech company that holds the rights to investigate and commercially exploit the pexa vec virus in europe. Oncolytic virus cancer therapy pipeline insights, 2019 report outlays comprehensive insights of present scenario and growth prospects across oncolytic virus cancer therapy. Jx594 is a targeted oncolytic and immunotherapeutic vaccinia virus engineered to express human granulocytemacrophage colony. But the determinants of resistance to pexa vec are mostly unknown. Jennerex announces science translational medicine publication.
Pexa vec was cytotoxic on myeloid cell lines in a dosedependent manner, and fluorescent imaging and qpcr revealed that pexa vec expression was low in ramos than im9 after 24 hrs and 48 hrs of. Oct 30, 2018 the companys lead clinicalstage programs are. The following software meets the requirements of the pexa subscriber security policy. An engineered oncolytic vaccinia virus, pexavec jx594tg6006 is armed with a gmcsf gene that promotes an antitumour immune response. Tg4010, a therapeutic vaccine against nonsmall cell lung cancer, pexavec, an oncolytic virus against liver cancer, and tg4001, a therapeutic vaccine against hpvpositive head and neck cancers. Transgene to present new clinical data on oncolytic virus. The trial was run in partnership with transgene, a french biotech company that holds the rights to investigate and commercially exploit the pexavec virus in europe. It triggers the breakdown of cancer cells through viral replication. The use of replicationcompetent viruses is an attractive strategy for tumor therapy after appropriate engineering so that they can preferentially and selectively propagate in cancer cells, thereby destroying tumor tissue, mainly via cell lysis, while leaving noncancerous tissues unharmed. Oncolytic virus therapy has recently been recognized as a promising new therapeutic approach for cancer treatment. We use cookies and similar technologies to recognize your repeat visits and preferences, to measure the effectiveness of campaigns, and improve our websites. Free antivirus download for pc avg virus protection software.
Sillajen explains pexavec trial failure it was the. Jun 17, 2019 while most of the ovs including t vec and pexa vec have demonstrated excellent safety profile in clinical settings, their antitumor efficacy has been modest so far 10,11,12. Currently, this virus is being assessed in a phase iii clinical trial, testing its efficacy by intratumoral injection of patients suffering from hepatocarcinoma clinicaltrials. The oncolytic vaccinia virus pexastimogene devacirepvec pexavec, jx594, armed with granulocytemacrophage colonystimulating factor gmcsfexpressing genes, is a representative lead from the. Pexa vec has undergone phase 1 and 2 testing alone and in combination with other therapies in adult patients, via both intratumoral and intravenous administration routes.
Jx594 is a modified copenhagen strain vaccinia poxvirus engineered by addition of the gmcsf gene and deletion of the thymidine kinase gene which limits viral replication to cells with high levels of thymidine kinase, typica. The rapid growth of tumors depends upon elevated levels of dntps, and while dntp concentrations are tightly regulated in normal cells, this control is often lost in transformed cells. First patient dosed in a phase 12 trial of pexavec. Cancerkilling virus acts by alerting immune system. Jan, 2015 pexa vec pexastimogene devacirepvec, jx594 is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocytemacrophage colonystimulating factor gmcsfdriven tumorspecific immunity. Edmund lattimes lab at thomas jefferson university and tested in clinical trials in melanoma patients. Jx594 is a targeted and armed oncolytic and immunotherapeutic vaccinia virus with disruption of the viral thymidine kinase gene and expression of. Aug 23, 2017 pexavec, whose name is derived from pexastimogene devacirepvec, is an oncolytic virus designed to kill cancer cells in three ways.
A small phase 2 trial of pexavec as a firstline therapy in liver cancer. Jx594 is an oncolytic virus also known as pexavec, inn pexastimogene devacirepvec originally constructed in dr. Pexastimogene devacirepvec sillajen biotherapeutics adisinsight. Jx594 has emerged as an attractive tool in oncolytic virotherapy. In a phase 2 trial of pexavec in firstline hcc, overall survival was improved in a dose dependent manner. Pexavec jx594 is an oncolytic immunotherapeutic based on an oncolytic.
The virus additionally expresses the gmcsf granulocytemacrophage colonystimulating factor cytokine to activate immune cells at the tumor site. Jx594 pexastimogene devacirepvec, pexa vec is an oncolytic vaccinia virus that is engineered to express an immuneactivating transgene, gmcsf, and that has the viral thymidine kinase gene disrupted. Pexavec demonstrates oncolytic and immunotherapeutic mechanisms of action. May 15, 20 oncolytic viruses cause direct cytolysis and cancerspecific immunity in preclinical models. The pexavec virus was originally developed by michael mastrangelo, md, and edmund lattime, ph. The goal of this study was to demonstrate induction of functional anticancer immunity that can lyse target cancer cells in humans. A comparative safety profile assessment of oncolytic virus. About pexavec pexavec jx594 is an oncolytic immunotherapeutic based on an oncolytic vaccinia virus armed with a gmcsf gene that promotes an antitumor immune response. Pexavec jx594 is an oncolytic immunotherapeutic based on an. Apr 30, 2014 the emerging therapeutic potential of the oncolytic immunotherapeutic pexa vec jx594 caroline j breitbach,1 john c bell,2,3 taeho hwang,1 david h kirn,1 james burke1 1sillajen inc, seoul, south korea. A detailed picture of the pipeline landscape is provided with summation of data from multiple sources with complete analysis by development stage. Ongoing trial exploring oncolytic virus pexavec in hcc. Another ov in advanced clinical trials is pexavec, a vaccinia virus vacv.
Tng, a biotech company that designs and develops virus based immunotherapies against cancers and infectious diseases, announces that new clinical data on the oncolytic virus pexa vec will be presented at the american society of clinical oncology asco annual meeting, taking place from 1 to 5 june in chicago. A chimeric poxvirus with j2r thymidine kinase deletion. Pexavec is an oncolytic immunotherapy product based on an oncolytic vaccinia virus expressing gmcsf. Engineered small pox may kill liver cancer sciencedaily. The pexa vec virus was originally developed by michael mastrangelo, md, and edmund lattime, phd, of thomas jefferson university in philadelphia, who engineered the harmless vaccinia virus to. Checkpoint inhibitors go viral nature biotechnology. Sillajen and abl europe expand strategic manufacturing. Talimogene laherparepvec tvec, which was approved in the united states in 2015 as a firstinclass oncolytic agent for metastatic melanoma, is an engineered herpes simplex virus with insertion of genes encoding granulocytemacrophage colonystimulating factor gmcsf as an immune adjuvant 1214. Jx594 showed impressive anticancer activity with low toxicity in preclinical and clinical studies. When will oncolytic viruses be approved for the treatment of. An oncolytic vaccinia virus armed with gmcsf pexavec was associated with a 15% objective response rate in patients with advanced hepatocellular carcinoma in. Much of our lives now take place online, and even in 2018, theres no such thing as being too careful. It promotes disruption of blood vessels, reducing a tumors blood supply. Cancer cells often bear p16 mutations, which result in increased rr activity detectable as r2 mrna, and an r1 hsv1 mutant was shown to replicate to higher levels in these cells.
Gene expression profiling of hematologic malignant cell. Its a shame, but, yes, you still need antivirus software. Optim are establishing use of oncolytic viruses as another tool in the cancer therapeutics. Sillajen announces commercial manufacturing agreement with. Pexavec pexastimogene devacirepvec, jx594 is an oncolytic. Based on the firms selective oncolytic vaccinia engineering solve platform, pexavec is designed to delete the thymidine kinase tk gene in cancer cells to target their common genetic defects. Transgene provides update on phocus study of pexavec in liver.
Pexavec pexastimogene devacirepvec, jx594 is an oncolytic immunotherapy oi based on the wyeth vaccinia vaccine strain which has been engineered for viral thymidine kinase tk gene inactivation, and expression of the human granulocytemonocyte colony stimulating factor hgmcsf and. Pdf gene expression profiling of hematologic malignant cell. Pexa vec demonstrates oncolytic and immunotherapeutic mechanisms of action. A chimeric poxvirus with j2r thymidine kinase deletion shows. Sorafenib, the standard of care in hcc, was approved by the fda in 2007. Immunization strategy with intratumoral injections of.
These viruses do not simply lyse cells to achieve their cancerkilling effects, but. The purpose of this study is to determine whether treatment with vaccinia virus based immune system therapy pexavec followed by sorafenib increases survival compared to treatment with sorafenib alone in patients with advanced liver cell cancer, who have not received prior systemic therapy. The ongoing phase iii phocus trial is comparing the oncolytic virus pexavec followed by sorafenib nexavar with sorafenib alone in patients with advanced hepatocellular carcinoma hcc. When will oncolytic viruses be approved for the treatment. Tng, a biotech company that designs and develops virusbased immunotherapies against cancers and infectious diseases, announces that new clinical data on the oncolytic virus pexavec will be presented at the american society of clinical oncology asco annual meeting, taking place from 1 to 5 june in chicago these results were obtained from a clinical. The pexa vec virus was originally developed by michael mastrangelo, md, and edmund lattime, ph. Combination of pexavec, checkpoint inhibitors to be tested. Phase 1 study of intratumoral pexavec jx594, an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients. Although pexavec has shown minimal adverse side effects, the tk deletion may not fully preclude virus replication in noncancerous metabolically active tissues, such as the liver. Jx594 pexastimogene devacirepvec, pexa vec is an oncolytic vaccinia virus that is engineered to express an immuneactivating transgene, gmcsf, and that has the viral thymidine kinase gene disrupted 26, 27. This feature of cancer cells has been used to advantage to develop oncolytic dna viruses. Pexavec is a genetically engineered virus that is used in the smallpox vaccine. Pexavec is designed to target and destroy cancer cells. Tg4010, a therapeutic vaccine against nonsmall cell lung cancer, pexavec, an oncolytic virus against liver cancer, and tg4001, a therapeutic.
The enhanced tumor specificity of tg6002, an armed. To improve the tumor selectivity and oncolytic activity, we developed a thymidine kinase tkdeleted cpxv expressing the suicide gene fcu1. Single intravenous preoperative administration of the oncolytic virus pexavec to prime antitumor immunity. About pexa vec pexa vec jx594 is an oncolytic immunotherapeutic based on an oncolytic vaccinia virus armed with a gmcsf gene that promotes an antitumor immune response. Pdf gene expression profiling of hematologic malignant.
Jan 30, 2018 based on the firms selective oncolytic vaccinia engineering solve platform, pexavec is designed to delete the thymidine kinase tk gene in cancer cells to target their common genetic defects. Dna viruses employ many different mechanisms to increase dntp levels in infected cells, because the low concentration of. Vaccinia viruses are enveloped doublestranded dna viruses belonging to the family of poxviridae and were utilized as vaccines for the eradication of smallpox. Jx594 showed impressive anticancer activity with low toxicity in. The first oncolytic virus to hit the market, tvec, was already approved by the fda in april 2015 for treatment of melanoma.
Effect of nacl on the stability of oncolytic vaccinia virus. The pexavec virus was originally developed by michael mastrangelo, md, and edmund lattime, phd, of thomas jefferson university in philadelphia, who. Single intravenous preoperative administration of the. Pexastimogene devacirepvec pexavec is a vaccinia virusbased oncolytic. The true potential of oncolytic viruses may lie in the treatment of. Virus could help treat advanced cancers medical xpress. Transgene to start phase ibii study with pexavec for. Transgene provides update on phocus study of pexavec in. Oncolytic live replicating virus, recombinant vaccinia virus gmgcf of classe 1, administered by intratumoral injection with fixeddosage regimen of 1x109 pfu 9. Our lead investigational product pexavec is a wyeth strain vaccinia virus.
Vaccinia virus is a descriptor in the national library of medicines controlled vocabulary thesaurus, mesh medical subject headings. Combination of pexavec, checkpoint inhibitors to be. The emerging therapeutic potential of the oncolytic. Oncolytic virus cancer therapy pipeline insights, 2019. Immunization strategy with intratumoral injections of pexa. Pexaveca modified vaccinia virus that has been engineered to. Pexavec is a groundbreaking oncolytic product with significant potential in the treatment of hcc, and we are excited to apply our 20 years of expertise in virus manufacturing to help bring this. Pexa vec is a strain that has its viral thymidine kinase tk gene deleted, thus requiring the virus to utilize nucleotide pools produced in metabolically active tumor cells. Gene expression profiling of hematologic malignant cell lines. Why school holiday care makes the christmas period a strain on working families we understand that when you go home work doesnt stop, and when youre at work, home doesnt stop, and so this is a way that we bring both parts of our lives closer together, linda hibberd, executive general manager people experience on how pexa s onsite school holiday care program helps our families achieve. But the determinants of resistance to pexavec are mostly unknown. Fda panels support approval of tvec in melanoma edit. Tumor microenvironment remodeling by intratumoral oncolytic.
Transgene to present new clinical data on oncolytic virus pexa. Descriptors are arranged in a hierarchical structure, which enables searching at various levels of specificity. Transgene sa 400 boulevard gonthier dandernach parc dinnovation cs80166 67405 illkirch graffenstaden cedex france phone. Single intravenous preoperative administration of the oncolytic virus pexavec to prime antitumor immunity samson. Pexavec has undergone phase 1 and 2 testing alone and in combination with other therapies in adult patients, via. Nec and transgene collaborate in the field of individualized.
Rational combination of oncolytic vaccinia virus and pdl1. The enhanced tumor specificity of tg6002, an armed oncolytic. May 15, 20 pexa vec exploits the unique characteristics of vaccinia, including its stealth extracellular enveloped form, which allows the virus to survive in the bloodstream in the presence of neutralizing. The study is a proof of concept, open label, multicentric, 2parts, phase i dose escalation trial. Pexa vec jx594 is a thymidine kinase geneinactivated oncolytic vaccinia virus engineered for the expression of transgenes encoding human granulocyte macrophage colonystimulating factor gmcsf and betagalactosidase. We treated hemoatologic malignant cells with pexavec and examined the geneexpression pattern of sensitive and resistant cells. An engineered oncolytic vaccinia virus, pexa vec jx594tg6006 is armed with a gmcsf gene that promotes an antitumour immune response. The purpose of this study was to develop methods to maximize the stability of pexavec. Pexavec pexastimogene devacirepvec is a modified vaccinia virus that has been engineered to express immuneboosting cytokine gmcsf. Jx594, a targeted oncolytic poxvirus for the treatment of. Sillajen and our partners have launched new clinical programs to explore the.
Pexavec, whose name is derived from pexastimogene devacirepvec, is an oncolytic virus designed to kill cancer cells in three ways. Pexavec clinical development program and solve platform pexavec is the most advanced product candidate from sillajens proprietary solve selective oncolytic vaccinia engineering platform. Apr 09, 20 pexa vec is a genetically engineered virus that is used in the smallpox vaccine. Deletion of apoptosis inhibitor f1l in vaccinia virus. Sillajen begins phase iii trial of pexavec for colon cancer. Gmcsf was the lead candidate in transgenes ovt program and the. Tng, a biotech company designing and developing virusbased immunotherapies for the treatment of solid tumors, today announces that the independent data monitoring committee idmc of the phocus study of pexavec in liver cancer has completed a planned interim futility analysis. While most of the ovs including tvec and pexavec have demonstrated excellent safety profile in clinical settings, their antitumor efficacy has been. Phase 1 study of intratumoral pexavec jx594, an oncolytic.
Pexavec has been engineered from the vaccinia virus, which has been used as a vaccine. Sillajen will supply pexavec for the clinical trial while pdl1 and ctla4. The emerging therapeutic potential of the oncolytic immunotherapeutic pexavec jx594 caroline j breitbach,1 john c bell,2,3 taeho hwang,1 david h kirn,1 james burke1 1sillajen inc, seoul, south korea. Pexa vec pexastimogene devacirepvec, jx594 is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocytemacrophage colonystimulating factor gmcsfdriven tumorspecific immunity. Tg4010, a therapeutic vaccine against nonsmall cell lung cancer, pexavec, an oncolytic virus. The first oncolytic virus to hit the market, t vec, was already approved by the fda in april 2015 for treatment of melanoma.
Oncolytic and immunotherapeutic vaccinia induces antibody. The oncolytic vaccinia virus pexastimogene devacirepvec pexa vec, jx594, armed with granulocytemacrophage colonystimulating factor gmcsfexpressing genes, is a representative lead from the. Jx594 pexastimogene devacirepvec, pexavec is an oncolytic vaccinia virus that is engineered to express an immuneactivating transgene, gmcsf, and that has the viral thymidine kinase gene disrupted 26, 27. Jx594 is an oncolytic virus originally constructed in dr. Oncolytic viruses cause direct cytolysis and cancerspecific immunity in preclinical models. Transgenes lead oncolytic virus pexavec triggers strong anti. We treated hemoatologic malignant cells with pexa vec and examined the geneexpression pattern of sensitive and resistant cells. The data further demonstrates that pexavec treatment induced an immune response against the tumour. Get protection against viruses, malware and spyware. Mar 27, 2017 an oncolytic vaccinia virus armed with gmcsf pexa vec was associated with a 15% objective response rate in patients with advanced hepatocellular carcinoma in a randomized phase ii clinical. Tg4010, a therapeutic vaccine against nonsmall cell lung cancer, pexa vec, an oncolytic virus against liver cancer, and tg4001, a therapeutic vaccine against hpvpositive head and neck cancers.
The gmo is a viral suspension of the recombinant virus jx594. In serumstarved cells, r1 mutants produce 10 to 1,000fold lower yields of virus and only a third of the dna synthesis of wildtype virus 153, 190, 191. In this study, we are proposing for the first time to evaluate the in vitro and in vivo oncolytic capacities of the cowpox virus cpxv. Due to its role in smallpox vaccination programs, the potential for immune.
The product candidate is also engineered to express gmcsf protein that complements cancer cell lysis, which results in tumour necrosis and. Pexavec jx594 is a specific cancertargeted oncolytic and immunotherapeutic vaccinia virus. Jx594 showed impressive anticancer activity withlowtoxicityinpreclinical andclinicalstudies. Bioinvent and transgene extend their collaboration to. The dosing schedules used by other oncolytic virus programs, if not. Jx594 is a targeted oncolytic and immunotherapeutic vaccinia virus engineered to express human granulocyte. Jx594 pexastimogene devacirepvec, pexavec is an oncolytic vaccinia virus that is engineered to express an immuneactivating transgene, gmcsf, and that has the viral thymidine kinase gene disrupted. A detailed picture of the pipeline landscape is provided with summation of data from multiple sources with complete analysis by development stage, mechanism of action. It is designed to selectively target and destroy cancer cells via three different mechanisms of action, including the lysis breakdown of cancer cells through viral replication, the reduction of the blood supply to tumours through vascular targeting and. Pexavec exploits the unique characteristics of vaccinia, including its stealth extracellular enveloped form, which allows the virus to survive in the bloodstream in the presence of neutralizing. Pexavec pexastimogene devacirepvec, jx594 is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocytemacrophage colonystimulating factor gmcsfdriven tumorspecific immunity. Transgenes programs utilize viral vector technology with the goal of. Apart from the direct oncolytic activity, oncolytic viruses such as pexavec have been shown to mediate tumor cell death via the induction of innate and adaptive.