MO-FG-BRA-04: Leveraging the Abscopal Effect Via New Design Radiotherapy Biomaterials Loaded with Immune Checkpoint Inhibitors

Authors

  • Hao Y,

    1. Univ Massachusetts Lowell, Lowell, MA
    2. Wentworth Institute of Technology, Boston, MA
    3. Dana Farber Cancer Institute, Boston, MA
    4. Harvard Medical School, Boston, MA
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  • Cifter G,

    1. Univ Massachusetts Lowell, Lowell, MA
    2. Wentworth Institute of Technology, Boston, MA
    3. Dana Farber Cancer Institute, Boston, MA
    4. Harvard Medical School, Boston, MA
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  • Altundal Y,

    1. Univ Massachusetts Lowell, Lowell, MA
    2. Wentworth Institute of Technology, Boston, MA
    3. Dana Farber Cancer Institute, Boston, MA
    4. Harvard Medical School, Boston, MA
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  • Sinha N,

    1. Univ Massachusetts Lowell, Lowell, MA
    2. Wentworth Institute of Technology, Boston, MA
    3. Dana Farber Cancer Institute, Boston, MA
    4. Harvard Medical School, Boston, MA
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  • Moreau M,

    1. Univ Massachusetts Lowell, Lowell, MA
    2. Wentworth Institute of Technology, Boston, MA
    3. Dana Farber Cancer Institute, Boston, MA
    4. Harvard Medical School, Boston, MA
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  • Sajo E,

    1. Univ Massachusetts Lowell, Lowell, MA
    2. Wentworth Institute of Technology, Boston, MA
    3. Dana Farber Cancer Institute, Boston, MA
    4. Harvard Medical School, Boston, MA
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  • Makrigiorgos G,

    1. Univ Massachusetts Lowell, Lowell, MA
    2. Wentworth Institute of Technology, Boston, MA
    3. Dana Farber Cancer Institute, Boston, MA
    4. Harvard Medical School, Boston, MA
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  • Ngwa W

    1. Univ Massachusetts Lowell, Lowell, MA
    2. Wentworth Institute of Technology, Boston, MA
    3. Dana Farber Cancer Institute, Boston, MA
    4. Harvard Medical School, Boston, MA
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Abstract

Purpose:

Studies show that stereotactic body radiation therapy (SBRT) of a primary tumor in combination with immune checkpoint inhibitors (ICI) could Result in an immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However toxicities due to repeated systematic administration of ICI have been shown to be a major obstacle in clinical trials. Towards overcoming these toxicity limitations, we investigate a potential new approach whereby the ICI are administered via sustained in-situ release from radiotherapy (RT) biomaterials (e.g. fiducials) coated with a polymer containing the ICI.

Methods:

New design RT biomaterials were prepared by coating commercially available spacers/fiducials with a biocompatible polymer (PLGA) film containing fluorescent nanoparticles of size needed to load the ICI. The release of the nanoparticles was investigated in-vitro. Meanwhile, an experimentally determined in- vivo nanoparticle diffusion coefficient was employed in analytic calculations based on Fick's second law to estimate the time for achieving the concentrations of ICI in the tumor draining lymph node (TDLN) that are needed to engender the abscopal effect during SBRT. The ICI investigated here was anti-CTLA-4 antibody (ipilimumab) at approved FDA concentrations.

Results:

Our in -vitro study results showed that RT biomaterials could be designed to achieve burst release of nanoparticles within one day. Meanwhile, our calculations indicate that for a 2 to 4 cm tumor it would take 4–22 days, respectively, following burst release, for the required concentration of ICI nanoparticles to accumulate in the TDLN during SBRT.

Conclusion:

Current investigations combining RT and immunotherapy involve repeated intravenous administration of ICI leading to significant systemic toxicities. Our preliminary results highlight a potential new approach for sustained in-situ release of the ICI from new design RT biomaterials. These results provide impetus for more studies to leverage the powerful abscopal effect, while minimizing systemic toxicities through the new approach.

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