Username


Password

Forgot Password?

Preview

Sign-in free and Explore the Exciting World of BiomedExperts:
  • Over 1.500.000 Profiles
  • More than 1.800 Organizations worldwide
  • State of the Art Network Visualizations
  • Manage your own Profile
  • Locate Experts in your Country/Region
  • Locate Experts in your 1. and 2. Level Network
  • Connect to Experts Worldwide

find experts for

Sign-in to see more
2001: Todo T; Martuza R L; Rabkin S D; Johnson P A
Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing.
Proceedings of the National Academy of Sciences of the United States of America 2001;98(11):6396-401.
Oncolytic herpes simplex virus type 1 (HSV-1) vectors are promising therapeutic agents for cancer. Their efficacy depends on the extent of both intratumoral viral replication and induction of a host antitumor immune response. To enhance these properties while employing ample safeguards, two conditionally replicating HSV-1 vectors, termed G47Delta and R47Delta, have been constructed by deleting the alpha47 gene and the promoter region of US11 from gamma34.5-deficient HSV-1 vectors, G207 and R3616, respectively. Because the alpha47 gene product is responsible for inhibiting the transporter associated with antigen presentation (TAP), its absence led to increased MHC class I expression in infected human cells. Moreover, some G47Delta-infected human melanoma cells exhibited enhanced stimulation of matched antitumor T cell activity. The deletion also places the late US11 gene under control of the immediate-early alpha47 promoter, which suppresses the reduced growth properties of gamma34.5-deficient mutants. G47Delta and R47Delta showed enhanced viral growth in a variety of cell lines, leading to higher virus yields and enhanced cytopathic effect in tumor cells. G47Delta was significantly more efficacious in vivo than its parent G207 at inhibiting tumor growth in both immune-competent and immune-deficient animal models. Yet, when inoculated into the brains of HSV-1-sensitive A/J mice at 2 x 10(6) plaque forming units, G47Delta was as safe as G207. These results suggest that G47Delta may have enhanced antitumor activity in humans.

Post to CiteULike

Sign in free and see...

Visualized networks:
See your personal network in
sophisticated graphical views
GeoTargeted Searches:
Locate experts around the world
and connect with global collaborators
Research Profiles:
See the visualized research activity
of experts around the globe
Sign-in to see more