Author of

• 14490

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  P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 14545

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    P2.04-055 - Anti-Glut-1 Antibody as a Novel Therapeutic Modality against Breast and Lung Cancers (ID 3158)

    09:30 - 09:30  |  Author(s): P. Nassarre
    • Abstract

    Background:
    The growth and survival of many tumors are dependent upon high glucose uptake to meets it energy needs. A family of glucose transporters proteins (GLUTs) facilitate glucose uptake by cancer cells. There are at least 12 known isoforms of glucose transporter proteins. These transporter proteins differ in their kinetics and its expression is tailored to the requirement of the individual cell type. Although more than one Glut transporter protein may be expressed by a particular tumor cell type, tumors frequently over express Glut-1 which is a high affinity glucose transporter protein allowing the tumor to internalized a relatively large amount of glucose. Indeed tumoral Glut-1 expression correlates with the intensity of glucose uptake seen in a PET scan. We have previously demonstrated that anti-Glut-1 monoclonal antibody inhibited proliferation and induced apoptosis in breast cancer and lung cancer cell lines in vitro. Here we report the results of our in vivo studies where we investigated the ability of anti-Glut-1 monoclonal antibody to retard tumor growth in orthotopically implanted MDAMB-231 cell line in female athymic nude mice. We also examined the ability of the Glut-1 antibody to augment the retardation of tumor growth induced by cisplatin, paclitaxel, tamoxifen, and trastuzumab in the study.
    
    Methods:
    MDA-MB-231 breast cancer cells were orthotopically implanted in female thymic nude mice. Cohorts of tumor bearing mice were treated with control solution (PBS) or different dose levels of anti-Glut 1 antibody through tail vein injections. The Glut-1 monoclonal antibody used in the studies detailed here was generated from the clone SPM498. Once an optimal dose of Glu-1 antibody was selected we tested its ability to augment the growth retardation induced by cisplatin, paclitaxel, tamoxifen and trastuzumab. Tumors were measured as treatments continued. At the sign of earliest distress the animals were sacrificed and the organs were harvested and examined for evidence of toxicity and metastases. The harvested tumors were then subjected to Western blot and immunohistochemical analysis to look for markers of apoptosis and proliferation. All the organs and peripheral blood were examined to look for evidence of organ toxicity as a consequence of treatment by the Glut-1 antibody.
    
    Results:
    Anti-Glut 1 antibody can be administered safely in high doses to mice. No consistent organ toxicities associated with Glut-1 treatment were observed. Specifically, there was no central nervous system side effects noted in the mice given that the brain accounts for approximately 30% of the total glucose consumption. Treatment with Anti-Glut-1 antibody did not demonstrate significant single agent activity; however an increase in survival was observed in mice treated with the combination of tamoxifen and the anti-Glut-1 antibody compared with tamoxifen alone. The results of the detailed analyses will be presented at the meeting.
    
    Conclusion:
    Our studies demonstrate that anti-Glut1 antibody can be safely administered to mice without major organ toxicity including CNS toxicity. It demonstrated limited anti-tumor efficacy as a single agent, but it shows an increased anti-tumor effect when combined with tamoxifen. Further studies evaluating the combination of anti-Glut-1 antibody with targeted and hormonal agents are warranted.