---
title: "In Situ Vaccination Plus Low‑Dose Targeted Radionuclide Therapy and Checkpoint Blockade in Murine"
id: "pubmed-42418729"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42418729"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42418729/"
doi: "10.1158/2326-6066.CIR-25-1475"
published_at: "2026-09-02T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# In Situ Vaccination Plus Low‑Dose Targeted Radionuclide Therapy and Checkpoint Blockade in Murine
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42418729
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42418729/)
- **DOI:** [10.1158/2326-6066.CIR-25-1475](https://doi.org/10.1158%2F2326-6066.CIR-25-1475)
- **Published At:** 2026-09-02T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study evaluated a combined immunotherapeutic strategy pairing a focal **in situ vaccination** (ISV) with systemic **dual immune checkpoint blockade** (anti‑PD‑L1 and anti‑CTLA‑4) and low‑dose **targeted radionuclide therapy (TRT)** in murine cancer models. - Rationale: focal radiotherapy can act as an ISV to prime adaptive antitumor immunity; however, priming alone often fails to propagate responses in metastatic disease. Low‑dose TRT was proposed to promote clonal expansion and propagation of antitumor immune responses. - Experimental approach: C57BL/6 mice were engrafted with primary and secondary tumors and given intravenous tumor cells to model advanced metastatic disease. Two poorly immunogenic, syngeneic tumor models were used: MOC2 head and neck squamous cell carcinoma and B78 melanoma. - Treatment components: ISV consisted of focal radiotherapy of the primary tumor plus intratumoral injection of a tumor‑specific monoclonal antibody and interleukin‑2 (IL‑2). Systemic therapy included **dual checkpoint blockade (DCP)** with anti‑PD‑L1 and anti‑CTLA‑4 antibodies. Low‑dose **TRT** was delivered systemically to promote immune propagation. - Comparisons: mice received monotherapy or double or triple combinations of low‑dose TRT, DCP, and primary tumor‑targeted ISV. - The abstract and available source text report the study design, tumor models, therapeutic components, and the overall hypothesis that combining ISV, TRT, and checkpoint inhibition could eradicate poorly immunogenic metastatic tumors in mice. - The provided source text is truncated before reporting experimental outcomes, quantitative results, survival data, response rates, immunologic correlates, toxicity, or statistical analyses; those details were not reported in the available source excerpt. - Affiliations and publication data are given: Cancer Immunol Res, 2026; multiple authors from the University of Wisconsin and other institutions; PMID 42418729; DOI 10.1158/2326-6066.CIR-25-1475. - Because outcome data and specific results are missing from the excerpt, conclusions about efficacy, mechanism, or translational implications cannot be stated beyond the authors' stated aims and experimental plan.
## Clinical Analysis & Structured Key Points
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In Situ Vaccination, Low-Dose Targeted Radionuclide Therapy, and Immune Checkpoint Inhibition Eradicate Poorly Immunogenic Metastatic Tumors in Murine Cancer Models [Trishna Debnath](https://pubmed.ncbi.nlm.nih.gov/?term=Debnath+T&cauthor_id=42418729)[#](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Won Jong Jin](https://pubmed.ncbi.nlm.nih.gov/?term=Jin+WJ&cauthor_id=42418729)[#](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Ravi B Patel](https://pubmed.ncbi.nlm.nih.gov/?term=Patel+RB&cauthor_id=42418729)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-2 "Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania."), [Peter M Carlson](https://pubmed.ncbi.nlm.nih.gov/?term=Carlson+PM&cauthor_id=42418729)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-3 "Department of Pediatrics, Emory University, Atlanta, Georgia."), [Md Mahfuzur Rahman](https://pubmed.ncbi.nlm.nih.gov/?term=Rahman+MM&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Tracy J Berg](https://pubmed.ncbi.nlm.nih.gov/?term=Berg+TJ&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Caroline P Kerr](https://pubmed.ncbi.nlm.nih.gov/?term=Kerr+CP&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Rene Welch Schwartz](https://pubmed.ncbi.nlm.nih.gov/?term=Schwartz+RW&cauthor_id=42418729)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-4 "Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Yujuan Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Meredith Hyun](https://pubmed.ncbi.nlm.nih.gov/?term=Hyun+M&cauthor_id=42418729)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-4 "Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Irene M Ong](https://pubmed.ncbi.nlm.nih.gov/?term=Ong+IM&cauthor_id=42418729)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-4 "Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Jamey P Weichert](https://pubmed.ncbi.nlm.nih.gov/?term=Weichert+JP&cauthor_id=42418729)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-5 "Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Reinier Hernandez](https://pubmed.ncbi.nlm.nih.gov/?term=Hernandez+R&cauthor_id=42418729)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-5 "Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-6 "Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Paul M Sondel](https://pubmed.ncbi.nlm.nih.gov/?term=Sondel+PM&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-7 "Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Zachary S Morris](https://pubmed.ncbi.nlm.nih.gov/?term=Morris+ZS&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#full-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.") Affiliations Expand ### Affiliations * 1 Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. * 2 Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. * 3 Department of Pediatrics, Emory University, Atlanta, Georgia. * 4 Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. * 5 Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. * 6 Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. * 7 Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. # Contributed equally. * PMID: **42418729** * DOI: [ 10.1158/2326-6066.CIR-25-1475 ](https://doi.org/10.1158/2326-6066.cir-25-1475) Item in Clipboard # In Situ Vaccination, Low-Dose Targeted Radionuclide Therapy, and Immune Checkpoint Inhibition Eradicate Poorly Immunogenic Metastatic Tumors in Murine Cancer Models Trishna Debnath et al. Cancer Immunol Res. 2026. Show details Display options Display options Format Abstract PubMed PMID Cancer Immunol Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cancer+Immunol+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Immunol+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42418729/) . 2026 Sep 2;14(9):1416-1432. doi: 10.1158/2326-6066.CIR-25-1475. ### Authors [Trishna Debnath](https://pubmed.ncbi.nlm.nih.gov/?term=Debnath+T&cauthor_id=42418729)[#](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Won Jong Jin](https://pubmed.ncbi.nlm.nih.gov/?term=Jin+WJ&cauthor_id=42418729)[#](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Ravi B Patel](https://pubmed.ncbi.nlm.nih.gov/?term=Patel+RB&cauthor_id=42418729)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-2 "Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania."), [Peter M Carlson](https://pubmed.ncbi.nlm.nih.gov/?term=Carlson+PM&cauthor_id=42418729)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-3 "Department of Pediatrics, Emory University, Atlanta, Georgia."), [Md Mahfuzur Rahman](https://pubmed.ncbi.nlm.nih.gov/?term=Rahman+MM&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Tracy J Berg](https://pubmed.ncbi.nlm.nih.gov/?term=Berg+TJ&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Caroline P Kerr](https://pubmed.ncbi.nlm.nih.gov/?term=Kerr+CP&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Rene Welch Schwartz](https://pubmed.ncbi.nlm.nih.gov/?term=Schwartz+RW&cauthor_id=42418729)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-4 "Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Yujuan Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Meredith Hyun](https://pubmed.ncbi.nlm.nih.gov/?term=Hyun+M&cauthor_id=42418729)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-4 "Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Irene M Ong](https://pubmed.ncbi.nlm.nih.gov/?term=Ong+IM&cauthor_id=42418729)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-4 "Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Jamey P Weichert](https://pubmed.ncbi.nlm.nih.gov/?term=Weichert+JP&cauthor_id=42418729)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-5 "Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Reinier Hernandez](https://pubmed.ncbi.nlm.nih.gov/?term=Hernandez+R&cauthor_id=42418729)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-5 "Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-6 "Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Paul M Sondel](https://pubmed.ncbi.nlm.nih.gov/?term=Sondel+PM&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-7 "Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin."), [Zachary S Morris](https://pubmed.ncbi.nlm.nih.gov/?term=Morris+ZS&cauthor_id=42418729)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42418729/#short-view-affiliation-1 "Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.") ### Affiliations * 1 Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. * 2 Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. * 3 Department of Pediatrics, Emory University, Atlanta, Georgia. * 4 Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. * 5 Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. * 6 Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. * 7 Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. # Contributed equally. * PMID: **42418729** * DOI: [ 10.1158/2326-6066.CIR-25-1475 ](https://doi.org/10.1158/2326-6066.cir-25-1475) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Focal radiotherapy can provide an in situ vaccine (ISV) effect that may prime adaptive antitumor immunity, which can be augmented by combination with intratumoral immune adjuvants and systemic immune checkpoint inhibition. However, propagation of an antitumor immune response is not consistently achieved in metastatic disease. Delivery of low-dose targeted radionuclide therapy (TRT) can promote clonal expansion and propagation of antitumor immune responses. Therefore, in this study, we combined dual immune checkpoint blockade (DCP; anti-PD-L1 and anti-CTLA-4) with ISV (focal radiotherapy with intratumoral injection of tumor-specific monoclonal antibody and IL2) to prime and with low-dose TRT to propagate antitumor immunity. C57BL/6 mice were engrafted with primary and secondary tumors and intravenously injected with tumor cells to model advanced metastatic disease. Mice with poorly immunogenic, syngeneic MOC2 head and neck squamous cell carcinomas or B78 melanomas received monotherapy or double or triple combinations of low-dose TRT, DCP, and primary tumor-targeted ISV. When compar
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