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Title: SU-F-T-59: The Effect of Radiotherapy Dose On Immunoadjuvants

Abstract

Purpose: Combining radiotherapy with immunotherapy is a promising approach to enhance treatment outcomes for cancer patients. This in-vitro study investigated which radiotherapy doses could adversely affect the function of anti-CD40 mAb, which is one of the key immunoadjuvants under investigations for priming such combination therapy. Methods: Human monocyte derived THP-1 cells were treated with 100ng/mL of PMA in chamber slides to differentiate into macrophage. The THP-1 differentiated macrophages were treated with 2uL/ml of the anti-CD40 mAb and incubated at 37°C and 5% CO2 for 24 hours. Anti-CD40 mAb treated cells were then irradiated at different doses of x-rays: (0, 2, 4, 6, 8, and 12) Gy using the Small Animal Radiotherapy Research Platform (SARRP). After radiation, the cells were left at 4°C for 2 hours followed by immunofluorescence assay. A Nikon inverted live-cell imaging system with fluorescence microscope was used to image the cells mounted on a slide fixed with Dapi. For comparison, an ELISA assay was performed with the antibody added to 3mL of PBS in multiple 10mm dishes. The 10mm dishes were irradiated at different x-ray dose: (0, 2, 4, 6, 8. 10, 12, and 15) Gy using the SARRP. Results: The anti-CD40 mAb activating the macrophages startsmore » to lose their viability due to radiation dose between 8Gy to 12Gy as indicated by the immunofluorescence assay. The ELISA assay, also indicated that such high doses could lead to loss of the mAb’s viability. Conclusion: This work suggests that high doses like those employed during Stereotactic Ablative Radiotherapy may affect the viability of immunoadjuvants such as anti-CD 40. This study avails in-vivo experiments combining radiotherapy with anti-cd40 to get synergistic outcomes, including in the treatment of metastatic disease.« less

Authors:
 [1];  [2];  [3];  [4]
  1. Dana Farber Cancer Institute, Boston, MA (United States)
  2. Dana-Farber Cancer Institute, Boston, Massachusetts (United States)
  3. University of Massachusetts Lowell, Lowell, MA (United States)
  4. Harvard Medical School, Boston, MA (United States)
Publication Date:
OSTI Identifier:
22642307
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ANIMALS; ANTIBODIES; BIOMEDICAL RADIOGRAPHY; CARBON DIOXIDE; ENZYME IMMUNOASSAY; FLUORESCENCE; IMAGES; IMMUNOTHERAPY; IN VITRO; IN VIVO; MACROPHAGES; METASTASES; MONOCYTES; NEOPLASMS; PATIENTS; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Moreau, M, Yasmin-Karim, S, Hao, Y, and Ngwa, W. SU-F-T-59: The Effect of Radiotherapy Dose On Immunoadjuvants. United States: N. p., 2016. Web. doi:10.1118/1.4956194.
Moreau, M, Yasmin-Karim, S, Hao, Y, & Ngwa, W. SU-F-T-59: The Effect of Radiotherapy Dose On Immunoadjuvants. United States. doi:10.1118/1.4956194.
Moreau, M, Yasmin-Karim, S, Hao, Y, and Ngwa, W. 2016. "SU-F-T-59: The Effect of Radiotherapy Dose On Immunoadjuvants". United States. doi:10.1118/1.4956194.
@article{osti_22642307,
title = {SU-F-T-59: The Effect of Radiotherapy Dose On Immunoadjuvants},
author = {Moreau, M and Yasmin-Karim, S and Hao, Y and Ngwa, W},
abstractNote = {Purpose: Combining radiotherapy with immunotherapy is a promising approach to enhance treatment outcomes for cancer patients. This in-vitro study investigated which radiotherapy doses could adversely affect the function of anti-CD40 mAb, which is one of the key immunoadjuvants under investigations for priming such combination therapy. Methods: Human monocyte derived THP-1 cells were treated with 100ng/mL of PMA in chamber slides to differentiate into macrophage. The THP-1 differentiated macrophages were treated with 2uL/ml of the anti-CD40 mAb and incubated at 37°C and 5% CO2 for 24 hours. Anti-CD40 mAb treated cells were then irradiated at different doses of x-rays: (0, 2, 4, 6, 8, and 12) Gy using the Small Animal Radiotherapy Research Platform (SARRP). After radiation, the cells were left at 4°C for 2 hours followed by immunofluorescence assay. A Nikon inverted live-cell imaging system with fluorescence microscope was used to image the cells mounted on a slide fixed with Dapi. For comparison, an ELISA assay was performed with the antibody added to 3mL of PBS in multiple 10mm dishes. The 10mm dishes were irradiated at different x-ray dose: (0, 2, 4, 6, 8. 10, 12, and 15) Gy using the SARRP. Results: The anti-CD40 mAb activating the macrophages starts to lose their viability due to radiation dose between 8Gy to 12Gy as indicated by the immunofluorescence assay. The ELISA assay, also indicated that such high doses could lead to loss of the mAb’s viability. Conclusion: This work suggests that high doses like those employed during Stereotactic Ablative Radiotherapy may affect the viability of immunoadjuvants such as anti-CD 40. This study avails in-vivo experiments combining radiotherapy with anti-cd40 to get synergistic outcomes, including in the treatment of metastatic disease.},
doi = {10.1118/1.4956194},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Conventional dose-effect relationships, such as those based upon the NSD or linear-quadratic concepts, do not account for dose inhomogeneities. Only a single dose value can be used in these equations and this can give rise to significant errors in the estimation of the tolerance dose in situations where dose distributions are inhomogeneous. This paper presents a method of integrating the biologically effective dose over the entire volume of each organ or tissue irradiated. Integral forms of the variable-exponent TDF and linear quadratic factor (LQF) models (ITDF and ILQF, respectively) can be used to determine whether or not any organ ormore » tissue in an irradiated volume has exceeded tolerance, regardless of dose distribution non-uniformity. Several examples are given with comparisons to solutions obtained by conventional dose-effect models.« less
  • Purpose: to evaluate the dosimetric and radiobiological consequences from having different gating windows, dose rates, and breathing patterns in gated VMAT lung radiotherapy. Methods: A novel 3D-printed moving phantom with central high and peripheral low tracer uptake regions was 4D FDG-PET/CT-scanned using ideal, patient-specific regular, and irregular breathing patterns. A scan of the stationary phantom was obtained as a reference. Target volumes corresponding to different uptake regions were delineated. Simultaneous integrated boost (SIB) 6 MV VMAT plans were produced for conventional and hypofractionated radiotherapy, using 30–70 and 100% cycle gating scenarios. Prescribed doses were 200 cGy with SIB to 240more » cGy to high uptake volume for conventional, and 800 with SIB to 900 cGy for hypofractionated plans. Dose rates of 600 MU/min (conventional and hypofractionated) and flattening filter free 1400 MU/min (hypofractionated) were used. Ion chamber measurements were performed to verify delivered doses. Vials with A549 cells placed in locations matching ion chamber measurements were irradiated using the same plans to measure clonogenic survival. Differences in survival for the different doses, dose rates, gating windows, and breathing patterns were analyzed. Results: Ion chamber measurements agreed within 3% of the planned dose, for all locations, breathing patterns and gating windows. Cell survival depended on dose alone, and not on gating window, breathing pattern, MU rate, or delivery time. The surviving fraction varied from approximately 40% at 2Gy to 1% for 9 Gy and was within statistical uncertainty relative to that observed for the stationary phantom. Conclusions: Use of gated VMAT in PET-driven SIB radiotherapy was validated using ion chamber measurements and cell survival assays for conventional and hypofractionated radiotherapy.« less
  • The influence of the dose-rate on tumor response in radiotherapy with 106-Ruthenium eye plaques has been investigated in an experimental tumor system. The identical total dose was applied within three different overall treatment times (42 hr, 192 hr and 312 hr), corresponding to dose-rates of 6.0 Gy/hr, 1.3 Gy/hr and 0.8 Gy/hr. The therapeutic outcome of brachytherapy varied significantly between the three groups of animals treated with different dose-rates. At a dose-rate of 1.3 Gy/hr all tumors were locally controlled, but no local control was observed when a dose-rate of 6.0 Gy/hr was delivered. 0.8 Gy/hr was less effective thanmore » 1.3 Gy/hr but more effective than 6.0 Gy/hr. These results were unexpected but they might be explained by an incomplete reoxygenation if the overall treatment time is too short (42 hr, dose-rate 6.0 Gy/hr) and by proliferation of tumor cells under treatment if the overall treatment time is too long (312 hr, 0.8 Gy/hr). This system is a biological model for treatment of uveal melanoma.« less