دورية أكاديمية
أعرض في EDS

Radiation to all macroscopic sites of tumor permits greater systemic antitumor response to in situ vaccination.

التفاصيل البيبلوغرافية
العنوان: Radiation to all macroscopic sites of tumor permits greater systemic antitumor response to in situ vaccination.
المؤلفون: Carlson PM; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Patel RB; Radiation Oncology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA., Birstler J; Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA., Rodriquez M; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Sun C; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Erbe AK; Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, USA., Bates AM; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Marsh I; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland, USA., Grudzinski J; Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA., Hernandez R; Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Pieper AA; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Feils AS; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Rakhmilevich AL; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, USA., Weichert JP; Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Bednarz BP; Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA., Sondel PM; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA zmorris@humonc.wisc.edu pmsondel@humonc.wisc.edu.; Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, USA., Morris ZS; Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA zmorris@humonc.wisc.edu pmsondel@humonc.wisc.edu.
المصدر: Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Jan; Vol. 11 (1).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Print Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd.
Original Publication: London : BioMed Central, 2013-
مواضيع طبية MeSH: CD8-Positive T-Lymphocytes* , Melanoma*, Mice ; Animals ; Immunotherapy/methods ; Immunologic Memory ; Vaccination
مستخلص: Background: The antitumor effects of external beam radiation therapy (EBRT) are mediated, in part, by an immune response. We have reported that a single fraction of 12 Gy EBRT combined with intratumoral anti-GD2 hu14.18-IL2 immunocytokine (IC) generates an effective in situ vaccine (ISV) against GD2-positive murine tumors. This ISV is effective in eradicating single tumors with sustained immune memory; however, it does not generate an adequate abscopal response against macroscopic distant tumors. Given the immune-stimulatory capacity of radiation therapy (RT), we hypothesized that delivering RT to all sites of disease would augment systemic antitumor responses to ISV.
Methods: We used a syngeneic B78 murine melanoma model consisting of a 'primary' flank tumor and a contralateral smaller 'secondary' flank tumor, treated with 12 Gy EBRT and intratumoral IC immunotherapy to the primary and additional EBRT to the secondary tumor. As a means of delivering RT to all sites of disease, both known and occult, we also used a novel alkylphosphocholine analog, NM600, conjugated to 90 Y as a targeted radionuclide therapy (TRT). Tumor growth, overall survival, and cause of death were measured. Flow cytometry was used to evaluate immune population changes in both tumors.
Results: Abscopal effects of local ISV were amplified by delivering as little as 2-6 Gy of EBRT to the secondary tumor. When the primary tumor ISV regimen was delivered in mice receiving 12 Gy EBRT to the secondary tumor, we observed improved overall survival and more disease-free mice with immune memory compared with either ISV or 12 Gy EBRT alone. Similarly, TRT combined with ISV resulted in improved overall survival and a trend towards reduced tumor growth rates when compared with either treatment alone. Using flow cytometry, we identified an influx of CD8 + T cells with a less exhausted phenotype in both the ISV-targeted primary and the distant secondary tumor following the combination of secondary tumor EBRT or TRT with primary tumor ISV.
Conclusions: We report a novel use for low-dose RT, not as a direct antitumor modality but as an immunomodulator capable of driving and expanding antitumor immunity against metastatic tumor sites following ISV.
Competing Interests: Competing interests: ZSM, JPW, RH, and JG have financial interests in Archeus Technologies. ZSM is a member of the Scientific Advisory Boards for Archeus Technologies and for Seneca Therapeutics. PMS is an unpaid medical advisor for Invenra. JPW is a cofounder, CSO, and director of Archeus Technologies, which holds the licence rights to NM600-related technologies. BPB and JG are cofounders of Voximetry, and BPB is the CSO. The following patents have been applied for or filed by the University of Wisconsin Alumni Research Foundation: US Patent 10,736,949, 'Radiohalogenated agents for in situ immune modulated cancer vaccination', with ZSM, PMS, JPW, and BPB as inventors; US Patent 10,751,430, 'Targeted radiotherapy chelates for in situ immune modulated cancer vaccination' with ZSM, PMS, JPW, BPB, and PMC as inventors; application no. 15/809,427, 'Using targeted radiotherapy to drive anti-tumor immune response to immunotherapies', ZSM, PMS, JPW, PMC, JG, RBP, and RH as inventors; and US 2011/0060602, 'A1 treatment planning system for radiopharmaceuticals', with BPB and JG as inventors.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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معلومات مُعتمدة: K08 CA241319 United States CA NCI NIH HHS; TL1 TR002375 United States TR NCATS NIH HHS; P30 CA014520 United States CA NCI NIH HHS; T32 GM008692 United States GM NIGMS NIH HHS; U01 CA233102 United States CA NCI NIH HHS; F30 CA228315 United States CA NCI NIH HHS; U54 CA232568 United States CA NCI NIH HHS; T32 GM140935 United States GM NIGMS NIH HHS; P01 CA250972 United States CA NCI NIH HHS; DP5 OD024576 United States OD NIH HHS; R35 CA197078 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Immunotherapy; Radiotherapy; Tumor Microenvironment
تواريخ الأحداث: Date Created: 20230113 Date Completed: 20230117 Latest Revision: 20231220
رمز التحديث: 20231220
مُعرف محوري في PubMed: PMC9843201
DOI: 10.1136/jitc-2022-005463
PMID: 36639155
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-1426
DOI:10.1136/jitc-2022-005463