Accession Number : ADA405395


Title :   Combination Antiangiogenic and Immunomodulatory Gene Therapy for Breast Cancer


Descriptive Note : Final rept. 1 May 1999-1 May 2002


Corporate Author : MOUNT SINAI SCHOOL OF MEDICINE NEW YORK


Personal Author(s) : Sauter, Bernhard


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a405395.pdf


Report Date : Jun 2002


Pagination or Media Count : 69


Abstract : Inhibition of angiogenesis has been shown to be an effective strategy in cancer therapy in mice. We constructed a recombinant adenovirus that expresses endostatin, which resulted in a significant delay of tumor progression of JC breast and Lewis lung carcinoma, and more importantly, in complete prevention of lung metastases formation in Lewis lung carcinoma. The inability to control pre-established tumors may be due to insufficient circulating endostatin levels or to inadequate local endostatin concentrations, both of which have been shown to be important for the anti-tumor effect of endostatin. Thus, we constructed a recombinant adenovirus expressing a murine Ig-endostatin fusion protein resulting in significantly higher circulating endostatin levels with improved anti-tumor activity. Furthermore, a tumor-targeted version of endostatin was made using homing peptides to activated endothelial cells (RGD, NGR) to increase directly endostatin concentrations in the tumor. Finally, conditionally replicating adenovirus (CRAD) targeted to the activated endothelium was very efficacious in selectively destroying 3-D capillary networks. In conclusion the present study clearly demonstrates the potential of vector-mediated antiangiogenic gene therapy in cancer. Changes in vector design resulting in higher transgene expression levels, tumor-targeted delivery of endostatin, or endothelial selective replication of adenovirus may prove to be an effective anti-cancer therapy.


Descriptors :   *ANGIOGENESIS , *BREAST CANCER , *GENES , CELLS(BIOLOGY) , ENDOTHELIUM , GENE THERAPY , INHIBITION , METASTASIS , NEOPLASMS , VECTOR ANALYSIS


Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE