FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3140413188> ?p ?o ?g. }

• W3140413188 abstract "Brain metastases develop in over 60% of advanced melanoma patients and negatively impact quality of life and prognosis. In a murine melanoma model, we previously showed that an in situ vaccination (ISV) regimen, combining radiation treatment and intratumoral (IT) injection of immunocytokine (IC: anti-GD2 antibody fused to IL2), along with the immune checkpoint inhibitor anti-CTLA-4, robustly eliminates peripheral flank tumors but only has modest effects on co-occurring intracranial tumors. In this study, we investigated the ability of low-dose radiation to the brain to potentiate anti-tumor immunity against a brain tumor when combined with ISV + anti-CTLA-4. B78 (GD2+, immunologically “cold”) melanoma tumor cells were implanted into the flank and the right striatum of the brain in C57BL/6 mice. Flank tumors (50–150 mm3) were treated following a previously optimized ISV regimen [radiation (12 Gy × 1, treatment day 1), IT-IC (50 µg daily, treatment days 6–10), and anti-CTLA-4 (100 µg, treatment days 3, 6, 9)]. Mice that additionally received whole-brain radiation treatment (WBRT, 4 Gy × 1) on day 15 demonstrated significantly increased survival compared to animals that received ISV + anti-CTLA-4 alone, WBRT alone or no treatment (control) (P < 0.001, log-rank test). Timing of WBRT was critical, as WBRT administration on day 1 did not significantly enhance survival compared to ISV + anti-CTLA-4, suggesting that the effect of WBRT on survival might be mediated through immune modulation and not just direct tumor cell cytotoxicity. Modest increases in T cells (CD8+ and CD4+) and monocytes/macrophages (F4/80+) but no changes in FOXP3+ regulatory T cells (Tregs), were observed in brain melanoma tumors with addition of WBRT (on day 15) to ISV + anti-CTLA-4. Cytokine multiplex immunoassay revealed distinct changes in both intracranial melanoma and contralateral normal brain with addition of WBRT (day 15) to ISV + anti-CTLA-4, with notable significant changes in pro-inflammatory (e.g., IFNγ, TNFα and LIX/CXCL5) and suppressive (e.g., IL10, IL13) cytokines as well as chemokines (e.g., IP-10/CXCL10 and MIG/CXCL9). We tested the ability of the alkylphosphocholine analog, NM600, to deliver immunomodulatory radiation to melanoma brain tumors as a targeted radionuclide therapy (TRT). Yttrium-86 (86Y) chelated to NM600 was delivered intravenously by tail vein to mice harboring flank and brain melanoma tumors, and PET imaging demonstrated specific accumulation up to 72 h at each tumor site (∼12:1 brain tumor/brain and ∼8:1 flank tumor/muscle). When NM600 was chelated to therapeutic β-particle-emitting 90Y and administered on treatment day 13, T-cell infiltration and cytokine profiles were altered in melanoma brain tumor, like that observed for WBRT. Overall, our results demonstrate that addition of low-dose radiation, timed appropriately with ISV administration to tumors outside the brain, significantly increases survival in animals co-harboring melanoma brain tumors. This observation has potentially important translational implications as a treatment strategy for increasing the response of tumors in the brain to systemically administered immunotherapies." @default.
• W3140413188 created "2021-04-13" @default.
• W3140413188 creator A5001986524 @default.
• W3140413188 creator A5005672422 @default.
• W3140413188 creator A5013731126 @default.
• W3140413188 creator A5017967519 @default.
• W3140413188 creator A5022153368 @default.
• W3140413188 creator A5025835765 @default.
• W3140413188 creator A5027244347 @default.
• W3140413188 creator A5033803080 @default.
• W3140413188 creator A5035945664 @default.
• W3140413188 creator A5037693950 @default.
• W3140413188 creator A5053858827 @default.
• W3140413188 creator A5054552399 @default.
• W3140413188 creator A5066902661 @default.
• W3140413188 creator A5071335391 @default.
• W3140413188 creator A5071431780 @default.
• W3140413188 creator A5074010402 @default.
• W3140413188 creator A5075107380 @default.
• W3140413188 creator A5078774800 @default.
• W3140413188 creator A5079824614 @default.
• W3140413188 creator A5089235637 @default.
• W3140413188 date "2021-04-07" @default.
• W3140413188 modified "2023-10-11" @default.
• W3140413188 title "Low-Dose Radiation Potentiates the Propagation of Anti-Tumor Immunity against Melanoma Tumor in the Brain after In Situ Vaccination at a Tumor outside the Brain" @default.
• W3140413188 cites W1254161066 @default.
• W3140413188 cites W1973699352 @default.
• W3140413188 cites W1975110303 @default.
• W3140413188 cites W2019427875 @default.
• W3140413188 cites W2022208959 @default.
• W3140413188 cites W2025421597 @default.
• W3140413188 cites W2026813736 @default.
• W3140413188 cites W2032166347 @default.
• W3140413188 cites W2040796340 @default.
• W3140413188 cites W2045683532 @default.
• W3140413188 cites W2066972199 @default.
• W3140413188 cites W2106882281 @default.
• W3140413188 cites W2107630189 @default.
• W3140413188 cites W2107838849 @default.
• W3140413188 cites W2108028653 @default.
• W3140413188 cites W2109347785 @default.
• W3140413188 cites W2112601576 @default.
• W3140413188 cites W2117878645 @default.
• W3140413188 cites W2131874142 @default.
• W3140413188 cites W2132390180 @default.
• W3140413188 cites W2137289789 @default.
• W3140413188 cites W2138985980 @default.
• W3140413188 cites W2147180300 @default.
• W3140413188 cites W2147652122 @default.
• W3140413188 cites W2148255040 @default.
• W3140413188 cites W2153875966 @default.
• W3140413188 cites W2157907127 @default.
• W3140413188 cites W2223346899 @default.
• W3140413188 cites W2275245978 @default.
• W3140413188 cites W2284512146 @default.
• W3140413188 cites W2346039915 @default.
• W3140413188 cites W2416333308 @default.
• W3140413188 cites W2515274402 @default.
• W3140413188 cites W2561312620 @default.
• W3140413188 cites W2570397462 @default.
• W3140413188 cites W2595863515 @default.
• W3140413188 cites W2610627565 @default.
• W3140413188 cites W2614237654 @default.
• W3140413188 cites W2617691667 @default.
• W3140413188 cites W2618641368 @default.
• W3140413188 cites W2624275086 @default.
• W3140413188 cites W2725989175 @default.
• W3140413188 cites W2743266319 @default.
• W3140413188 cites W2753027941 @default.
• W3140413188 cites W2765157849 @default.
• W3140413188 cites W2768550912 @default.
• W3140413188 cites W2788422234 @default.
• W3140413188 cites W2794155951 @default.
• W3140413188 cites W2794627893 @default.
• W3140413188 cites W2799371485 @default.
• W3140413188 cites W2802922010 @default.
• W3140413188 cites W2805970585 @default.
• W3140413188 cites W2890639244 @default.
• W3140413188 cites W2890879185 @default.
• W3140413188 cites W2891407885 @default.
• W3140413188 cites W2898394368 @default.
• W3140413188 cites W2911645108 @default.
• W3140413188 cites W2917980132 @default.
• W3140413188 cites W2924637436 @default.
• W3140413188 cites W2926293214 @default.
• W3140413188 cites W2927262639 @default.
• W3140413188 cites W2930789207 @default.
• W3140413188 cites W2938341288 @default.
• W3140413188 cites W2949498852 @default.
• W3140413188 cites W2990014697 @default.
• W3140413188 cites W2996516775 @default.
• W3140413188 cites W3013766663 @default.
• W3140413188 cites W3014876791 @default.
• W3140413188 cites W3042608708 @default.
• W3140413188 cites W4211223138 @default.
• W3140413188 cites W4211260961 @default.
• W3140413188 cites W4233319789 @default.
• W3140413188 cites W4236102117 @default.
• W3140413188 doi "https://doi.org/10.1667/rade-20-00237.1" @default.
• W3140413188 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8259713" @default.

• next