ArticleInternational journal of radiation oncology, biology, physics2014
Tumor radiation therapy creates therapeutic vaccine responses to the colorectal cancer antigen GUCY2C.
Article in International journal of radiation oncology, biology, physics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- Probiotics lead to a new frontier in tumor fighting: tumor vaccines based on probiotics.Journal of translational medicine · 2025Review
- Challenges to addressing the unmet medical needs for immunotherapy targeting cold colorectal cancer.World journal of gastrointestinal oncology · 2023Article
- Radiotherapy/Chemotherapy-Immunotherapy for Cancer Management: From Mechanisms to Clinical Implications.Oxidative medicine and cellular longevity · 2023Review
- Targeting gastrointestinal cancers with chimeric antigen receptor (CAR)-T cell therapy.Cancer biology & therapy · 2022Article
- A liposomal RNA vaccine inducing neoantigen-specific CD4Oncoimmunology · 2020Article
- Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients.Journal for immunotherapy of cancer · 2019Article
- Primary Tumor Site Specificity is Preserved in Patient-Derived Tumor Xenograft Models.Frontiers in genetics · 2019Article
- Prime-Boost Immunization Eliminates Metastatic Colorectal Cancer by Producing High-Avidity Effector CD8Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Immunotherapy Combined with Large Fractions of Radiotherapy: Stereotactic Radiosurgery for Brain Metastases-Implications for Intraoperative Radiotherapy after Resection.Frontiers in oncology · 2017Review
- The Immunoregulatory Potential of Particle Radiation in Cancer Therapy.Frontiers in immunology · 2017Article
- Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2016Review
- Drug development: Mix and match.Nature · 2015Article
- Radiation meets immunotherapy - a perfect match in the era of combination therapy?International journal of radiation biology · 2015Review
- GUCY2C lysosomotropic endocytosis delivers immunotoxin therapy to metastatic colorectal cancer.Oncotarget · 2014Article
- Non-thermal plasma induces immunogenic cell deathOncoimmunologyArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeRadiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. METHODS AND MATERIALS: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence.
resultsThe specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells.
conclusionsOptimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance of modality sequence optimization before the initiation of clinical trials of RT and IT to maximize immune and antitumor responses.
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