Pexastimogene devacirepvec

Key takeaways

Pexastimogene devacirepvec belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Pexastimogene devacirepvec to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Pexastimogene devacirepvec from memory before moving on to harder problems.

Reference excerpt

JX-594 is an oncolytic virus is designed to target and destroy cancer cells. It is also known as Pexa-Vec, INN pexastimogene devacirepvec) and was constructed in Dr. Edmund Lattime's lab at Thomas Jefferson University, tested in clinical trials on melanoma patients, and licensed and further developed by SillaJen. JX-594 is a modified Copenhagen strain (or Wyeth strain) vaccinia poxvirus engineered by addition of the GM-CSF gene and deletion of the thymidine kinase gene which limits viral replication to cells with high levels of thymidine kinase, typically seen in cancer cells with a mutated RAS or p53 gene. The virus also has the LacZ gene insertion under control of the p7.5 promoter. The virus kills the infected/cancer cells by lysis and also expresses GM-CSF which may help initiate an anti-tumour immune response.

It has orphan drug designation from US Food and Drug Administration and EUMA for the treatment of hepatocellular carcinoma (liver cancer). In clinical trials doses have been administered by intratumoral or intravenous injection.

Technology Pexa-Vec (JX-594) is the most advanced product candidate from SillaJen's proprietary SOLVE™ (Selective Oncolytic Vaccinia Engineering) platform. SOLVE is used to optimize virus targeting to specific cancer types, to select transgenes to include into the viral genome, and to optimize viral infection and/or replication selectively through targeted mutations. Oncolytic viruses could have 3-prolonged attack on cancer: direct cell lysis with replication and spread, immune activation, and antivascular

Tumor selective intratumoral replication of the virus leads to lysis of the infected cancer cell and spread to adjacent cancer cells Induction of tumor-specific cytotoxic T-lymphocytes and “arming” for expression of therapeutic transgene products (e.g. GM-CSF) enhance immune response to the tumor Blood flow to tumors can be blocked following intratumoral replication and spreadJX-900 (VVDD): VVDD Platform: Next-gen enhanced oncolytic immunotherapy. JX-900 (VVDD): VVDD Platform: Next-gen enhanced oncolytic immunotherapy.

JX-900 is a series of modified vaccinia vaccine (Western Reserve strain) with enhanced oncolytic potency Attenuation via “Double-Deletion” : thymidine kinase and vaccinia growth factor gene inactivation JX-929 (vvDD expressing CD for 5-FU pro-drug) experience in solid tumors (CRC and melanoma) JX-970 (vvDD expressing granulocyte-macrophage colony-stimulating factor) next generation of the VVDD series

Clinical trials A phase 3 randomized, open-label, clinical trial of Pexa-Vec plus sorafenib versus sorafenib is being conducted on patients with advanced hepatocellular carcinoma who have not previously received any systemic therapy. The study is being done to determine and compare overall survival for patients in the two treatment arms. The study is Sponsored by SillaJen, Inc.

Mechanism of Action of Pexa-Vec (Jx-594) The experimental therapy, Pexa-Vec, is an attenuated vaccinia virus engineered to stimulate anti-tumor immunity and directly lyse tumor cells. Pexa-Vec has cancer selectivity through the deactivation of its thymidine kinase gene, and it has been engineered to express the granulocyte-macrophage colony-stimulating factor gene to stimulate a systemic anti-tumor immune response. Researchers believe that Pexa-Vec may be a systemic treatment of hepatocellular carcinoma by inducing tumor necrosis and shrinkage of both injected and non-injected tumors after direct intratumoral delivery. Final data from a randomized dose-ranging phase 2 study of Pexa-Vec in mainly sorafenib naïve patients with advanced hepatocellular carcinoma demonstrated that the risk of death for patients who received Pexa-Vec at the high dose was markedly reduced (by nearly 60 percent; hazard ratio = 0.41) when compared to patients randomized to a low dose control (one-tenth of the high dose). The median overall survival for high and low dose groups was 14.1 months versus 6.7 months, respectively (p = 0.020 for superiority of the high dose). Pexa-Vec was well tolerated, with patients experiencing transient flu-like symptoms that generally resolved within 24 hours.[1] As of June 2018, these are the clinical trials investigating Pexa-Vec.[2]

Study Design Participants will be randomly assigned to one of two treatment arms, having an equal chance of receiving either Pexa-Vec followed by sorafenib, or sorafenib alone.

Arm A: Pexa-Vec followed by sorafenib Participants will visit the study center approximately 14 times over 18 weeks. All Pexa-Vec treatments (3) will be given by intratumoral injections into liver tumors. Following Pexa-Vec injection series completion, patients will receive sorafenib starting at week 6 of the study

Arm B: sorafenib Participants will visit the study center approximately 12 times over 18 weeks and receive sorafenib as per standard of care.

Pipeline candidates

JX-Next Generation Novel oncolytic viruses in SillaJen pipeline are engineered through the Selective Oncolytic Vaccinia Engineering (SOLVE) platform.

JX-929 JX-929 is derived from Western Reserve strain vaccinia virus. JX-929's tumor selectivity has been optimized through deletion of thymidine kinase and vaccinia growth factor. JX-929 has been administered as a monotherapy to patients with breast, colorectal, and pancreatic cancer via intratumoral & intravenous injections in a Phase 1, dose escalation clinical trial. This Phase 1 study showed delivery to and replication within tumors both IT and IV.

JX-970 JX-970 is also derived from a Western Reserve strain vaccinia virus and utilizes the same tumor selectivity mechanisms as JX-929. In addition, it expresses granulocyte-macrophage colony-stimulating factor to stimulate immune responses. In nonclinical studies, the JX-970 backbone exerted a tumor debulking effect and at the same time demonstrated a selective preference for tumor tissues. The precursor of JX-970 is JX-963 which demonstrated efficacy in pre-clinical studies.

References

Worked examples

Example 1 — a first encounter with Pexastimogene devacirepvec

Start with the simplest possible case. Write down what Pexastimogene devacirepvec claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Pexastimogene devacirepvec before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Pexastimogene devacirepvec ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Pexastimogene devacirepvec

In research: Pexastimogene devacirepvec appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Pexastimogene devacirepvec in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Pexastimogene devacirepvec is common in secondary-school and first-year university syllabi. It links to neighbouring topics Experimental cancer treatments, Virotherapy, so understanding it makes those chapters shorter.
In everyday life: Look for Pexastimogene devacirepvec outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Pexastimogene devacirepvec in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Pexastimogene devacirepvec means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Pexastimogene devacirepvec out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Pexastimogene devacirepvec in simple terms?

JX-594 is an oncolytic virus is designed to target and destroy cancer cells. It is also known as Pexa-Vec, INN pexastimogene devacirepvec) and was constructed in Dr.

Why does Pexastimogene devacirepvec matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Pexastimogene devacirepvec?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Pexastimogene devacirepvec.