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John Frances Marshall



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    P1.03 - Biology (Not CME Accredited Session) (ID 935)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.03-19 - Antibody Blockade of Integrin Alpha-V-Beta-6 (avb6) as a Novel Treatment for NSCLC (ID 12193)

      16:45 - 18:00  |  Author(s): John Frances Marshall

      • Abstract
      • Slides

      Background

      Expression of integrin alpha-v-beta-6 (αvβ6) is restricted to epithelial cells. It is weak or absent on normal tissues unless tissue re-modelling occurs in situations like fibrosis and cancer. It promotes multiple pro-tumorigenic processes, including cell migration, invasion and the activation of latent TGFβ1. Strong expression in multiple cancers is associated with poorer prognosis including a reported 54% of non-small cell lung cancers (NSCLC). Antibody blockade of αvβ6 with 264RAD antibody reduces tumour growth in breast and pancreatic cancer mouse models. The effect of αvβ6 blockade on NSCLC is unknown.

      Mutations in KRAS occur in approximately 30% of NSCLC. In the well described conditional transgenic KrasLSLG12D+/-; P53fl/fl (KP) mouse model of lung cancer, adenocarcinomas develop due to adenoviral cre-recombinase activation of a K-RasG12D allele and loss of P53. Tumour sections from this model show β6 expression (evidenced by αvβ6-specific SPECT imaging and pathology).

      We investigated the effect of αvβ6 blockade in the KP mouse.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      KP mice tumours were initiated by intra-tracheal instillation of adenoviral cre-recombinase. At 10 weeks, when significant disease was present (confirmed by MRI) treatment commenced. Four treatment groups of n=10 were allocated to either: 264RAD(10mg/kg, ip twice weekly); 264RAD (10mg/kg, ip twice weekly) + cisplatin(6mg/kg, weekly for 3 weeks); cisplatin(6mg/kg, weekly for 3 weeks); or IgG (10mg/kg, ip twice weekly). Progression (MRI) and survival was monitored.

      wlcc abstract 2018.jpg

      4c3880bb027f159e801041b1021e88e8 Result

      Results support using MRI as the preferred method to monitor tumour growth. Survival, lung pathology studies and imaging data will be presented at the meeting.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We have established a method to study the effects of αvβ6 blockade on lung tumour growth in vivo and are developing an imaging strategy using both MRI and SPECT to analyse mouse lung tumour growth in a manner that best mirrors human studies.

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