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H.M. Kelly



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      68P - In vivo study of a novel chemoablative, thermoresponsive hydrogel for intratumoural administration in a murine A549 xenograft model (ID 280)

      12:30 - 13:00  |  Author(s): H.M. Kelly

      • Abstract

      Background:
      Direct intratumoural (IT) injection of chemotherapeutics into solid tumours has potential to achieve high local concentrations, reducing systemic toxicity and off target side effects. However, this approach is limited by rapid drug clearance from the tumour, resulting in inaccurate and unpredictable dosing. Thermoresponsive hydrogels undergo a characteristic phase change in response to temperature. This allows for minimally invasive administration of a liquid via needle/catheter into the tumour, with localisation and retention following gelation at physiological temperatures. Drug loading of hydrogels facilitates localised, controlled delivery of chemotherapeutics to the tumour, with reduced off site toxicity.

      Methods:
      Preclinical assessment of blank and drug loaded formulations was conducted in a murine A549 xenograft model (approved by the RCSI ethics committee). 1 × 10[6] A549-luciferase cells were subcutaneously injected into the right flank of female Athymic Nude-Foxn1[nu] mice (n = 6 per group). At a tumour volume of approx. 250 mm[3], 100 μL of hydrogel (blank or drug loaded) or saline was injected IT using a 22G needle. Tumour growth was assessed using callipers and an IVIS® Spectrum in vivo imaging system over 14 days. On day 14, mice were sacrificed; tumours, liver and kidney excised, fixed and embedded in paraffin for histological and immunohistochemistry studies.

      Results:
      Two hours after IT injection, IVIS® imaging indicated localisation and retention of the hydrogel at injection site. At day 7 and 14 following blank or drug loaded hydrogel treatment, a significant reduction in tumour growth was observed compared to saline (p = 0.001). Retention of the hydrogel at the tumour site for up to 14 days was observed in ex vivo tumour tissue. No change in welfare scoring was observed during the study, with 100% survival at day 14, indicating treatment did not result in acute off site toxicity.

      Conclusions:
      Preliminary preclinical studies have shown the blank and drug loaded hydrogels significantly reduce tumour growth. Further studies are required to fully elucidate the underlying mechanism of action. IT administration of this formulation may represent a potential new adjuvant approach in lung cancer treatment.

      Clinical trial identification:


      Legal entity responsible for the study:
      Royal College of Surgeons in Ireland

      Funding:
      Enterprise Ireland

      Disclosure:
      All authors have declared no conflicts of interest.