A (oncolytic) virus that only spread to Her2+ cell.

[fullofbeans]

Interesting paper and I think virus may well be the next big things in cancer treatment. This Herpes virus targets Her2+


Menotti L, Cerretani A, Hengel H, Campadelli-Fiume G.
Source

Department of Experimental Pathology, Section on Microbiology and Virology, Alma Mater Studiorum, University of Bologna, Via San Giacomo, 12, 40126 Bologna, Italy.

Abstract

A novel frontier in the treatment of tumors that are difficult to treat is oncolytic virotherapy, in which a replication-competent virus selectively infects and destroys tumor cells. Herpes simplex virus (HSV) represents a particularly attractive system. Effective retargeting to tumor-specific receptors has been achieved by insertion in gD of heterologous ligands. Previously, our laboratory generated an HSV retargeted to human epidermal growth factor receptor 2 (HER2), a receptor overexpressed in about one-third of mammary tumors and in some ovarian tumors. HER2 overexpression correlates with increased metastaticity and poor prognosis. Because HER2 has no natural ligand, the inserted ligand was a single-chain antibody to HER2. The objective of this work was to genetically engineer an HSV that selectively targets the HER2-expressing tumor cells and that has lost the ability to enter cells through the natural gD receptors, HVEM and nectin1. Detargeting from nectin1 was attempted by two different strategies, point mutations and insertion of the single-chain antibody at a site in gD different from previously described sites of insertion. We report that point mutations at gD amino acids 34, 215, 222, and 223 failed to generate a nectin1-detargeted HSV. An HSV simultaneously detargeted from nectin1 and HVEM and retargeted to HER2 was successfully engineered by moving the site of single-chain antibody insertion at residue 39, i.e., in front of the nectin1-interacting surface and not lateral to it, and by deleting amino acid residues 6 to 38. The resulting recombinant, R-LM113, entered cells and spread from cell to cell solely via HER2.

PMID:18684832 [PubMed - indexed for MEDLINE]
PMCID: PMC2566291
Free PMC Article

[StephN]

Dear "Work in Progress" -
Very much hope that the "work" is having some kind of headway in finding your way back to NED.

That is such an interesting concept and we have spoken about viruses here before. Looks like they have gotten to the intracellular domain and mined it pretty well to come up with this form of possible treatment.

I know you are looking for the next "smart bomb" and hope it comes in the near future.

[pibikay]

Sinsrely hope that the research fructifies

[mamacze]

It seems like we keep coming back to virus therapy in our research; I know that a lot of vaccine researchers use viral vectors to introduce the her 2 protein in their vaccines. Thank you for sharing!
Kim from CT

[KDR]

An oncologist I met recently while searching out the T-DM1 clincial trial said, "We're still not sure if this is a virus (meaning HER2)." I'm tending to lean this way. I also think it would be prudent for every oncologist to search out any and all significant viruses a patient has had: HPV, Herpes, Epstein-Barr, Lyme's, et al. When I see my regular onco next week, I will ask this question.
Karen

['lizbeth]

Which Herpes virus is this? Chicken pox?