Frontiers in Oncology (Oct 2021)
Optimizing In Situ Vaccination During Radiotherapy
- Sayeda Yasmin-Karim,
- Sayeda Yasmin-Karim,
- Sayeda Yasmin-Karim,
- Jana Wood,
- Jana Wood,
- Jana Wood,
- Jana Wood,
- Johanna Wirtz,
- Johanna Wirtz,
- Johanna Wirtz,
- Johanna Wirtz,
- Michele Moreau,
- Michele Moreau,
- Michele Moreau,
- Michele Moreau,
- Michele Moreau,
- Noella Bih,
- Noella Bih,
- Noella Bih,
- William Swanson,
- William Swanson,
- William Swanson,
- William Swanson,
- Ashley Muflam,
- Victoria Ainsworth,
- Victoria Ainsworth,
- Victoria Ainsworth,
- Victoria Ainsworth,
- Bashkim Ziberi,
- Bashkim Ziberi,
- Bashkim Ziberi,
- Bashkim Ziberi,
- Wilfred Ngwa,
- Wilfred Ngwa,
- Wilfred Ngwa,
- Wilfred Ngwa
Affiliations
- Sayeda Yasmin-Karim
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- Sayeda Yasmin-Karim
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- Sayeda Yasmin-Karim
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- Jana Wood
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- Jana Wood
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- Jana Wood
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- Jana Wood
- Department of Immunology and Microbiology, University of Veternary Medicine and Pharmacy in Kosice, Kosice, Slovakia
- Johanna Wirtz
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- Johanna Wirtz
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- Johanna Wirtz
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- Johanna Wirtz
- Medical Faculty, University of Ulm, Ulm, Germany
- Michele Moreau
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- Michele Moreau
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- Michele Moreau
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- Michele Moreau
- Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA, United States
- Michele Moreau
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, United States
- Noella Bih
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- Noella Bih
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- Noella Bih
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- William Swanson
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- William Swanson
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- William Swanson
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- William Swanson
- Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA, United States
- Ashley Muflam
- Department of Library and Information Science, Rutgers University New Brunswick, New Brunswick, NJ, United States
- Victoria Ainsworth
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- Victoria Ainsworth
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- Victoria Ainsworth
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- Victoria Ainsworth
- Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA, United States
- Bashkim Ziberi
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- Bashkim Ziberi
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- Bashkim Ziberi
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- Bashkim Ziberi
- Department of Physics, University of Tetova, Tetova, North Macedonia
- Wilfred Ngwa
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States
- Wilfred Ngwa
- Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, United States
- Wilfred Ngwa
- Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States
- Wilfred Ngwa
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, United States
- DOI
- https://doi.org/10.3389/fonc.2021.711078
- Journal volume & issue
-
Vol. 11
Abstract
Effective in situ cancer vaccines require both a means of tumor cell death and a source of adjuvant to activate local dendritic cells. Studies have shown that the use of radiotherapy (RT) to induce tumor cell death and anti-CD40 to activate dendritic cells can result in in situ vaccination in animal models. Here, investigations are carried out on potential strategies to enhance such in situ vaccination. Strategies investigated include the use of smart immunogenic biomaterials (IBM) loaded with anti-CD40 in different tumor types including immunologically cold tumors like pancreatic and prostate tumors. The use of downstream checkpoint inhibitors to further boost such in situ vaccination is also examined. Results indicate that the use of IBM to deliver the anti-CD40 significantly enhances the effectiveness of in situ vaccination with anti-CD40 compared with direct injection in pancreatic and prostate cancers (p < 0.001 and p < 0.0001, respectively). This finding is consistent with significant increase in infiltration of antigen-presenting cells in the treated tumor, and significant increase in the infiltration of CD8+ cytotoxic T lymphocyte into distant untreated tumors. Moreover, in situ vaccination with IBM is consistently observed across different tumor types. Meanwhile, the addition of downstream immune checkpoint inhibitors further enhances overall survival when using the IBM approach. Overall, the findings highlight potential avenues for enhancing in situ vaccination when combining radiotherapy with anti-CD40.
Keywords
