ArticleOncotarget2019
Low-dose metronomic cyclophosphamide complements the actions of an intratumoral C-class CpG TLR9 agonist to potentiate innate immunity and drive potent T cell-mediated anti-tumor responses.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Effects of the Alkylating Agent Cyclophosphamide in Potentiating Anti-Tumor Immunity.International journal of molecular sciences · 2025Review
- Systematic identification and characterization of high efficiency Cas9 guide RNAs for therapeutic targeting of ADAR.PloS one · 2025Article
- A Combination Therapy of Cyclophosphamide and Immunomodulating Agents in Cancer.Current cancer drug targets · 2025Review
- Optimizing cancer therapy: a review of the multifaceted effects of metronomic chemotherapy.Frontiers in cell and developmental biology · 2024Review
- Macrophages in tumor cell migration and metastasis.Frontiers in immunology · 2024Review
- Invention and characterization of a systemically administered, attenuated and killed bacteria-based multiple immune receptor agonist for anti-tumor immunotherapy.Frontiers in immunology · 2024Article
- Review
- Potential of mRNA vaccines to become versatile cancer vaccines.World journal of clinical oncology · 2022Review
- Clinical trials of immunotherapy in triple-negative breast cancer.Breast cancer research and treatment · 2022Review
- Engineered nanomaterials trigger abscopal effect in immunotherapy of metastatic cancers.Frontiers in bioengineering and biotechnology · 2022Review
- Chronometric Administration of Cyclophosphamide and a Double-Stranded DNA-Mix at Interstrand Crosslinks Repair Timing, Called "Karanahan" Therapy, Is Highly Efficient in a Weakly Immunogenic Lewis Carcinoma Model.Pathology oncology research : POR · 2022Article
- A Squalene-Based Nanoemulsion for Therapeutic Delivery of Resiquimod.Pharmaceutics · 2021Article
- Immune System Alterations in Multiple Myeloma: Molecular Mechanisms and Therapeutic Strategies to Reverse Immunosuppression.Cancers · 2021Review
- CpG Adjuvant in Allergen-Specific Immunotherapy: Finding the Sweet Spot for the Induction of Immune Tolerance.Frontiers in immunology · 2021Review
- Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists.Cancers · 2020Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The synthetic oligonucleotide SD-101 is a potent and specific agonist for toll-like receptor 9. Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade. To build upon this strategy, we studied the enhancement of SD-101 activities by combination with low-dose cyclophosphamide, a well-characterized agent with potentially complementary activities. In multiple mouse tumor models, we demonstrate substantial anti-tumor activity of the combination, compared to each single agent. Combination therapy generated CD8+ T cell dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in very large tumors. Mechanistic studies encompassing global gene expression changes and characterization of immune cell infiltrates show the rapid, sequential induction of innate and adaptive responses and identify discrete contributions of SD-101 and cyclophosphamide. Importantly, these changes were prominent in tumors not injected directly with SD-101. Combination treatment resulted in creation of a permissive environment for a systemic anti-tumor immune response, including a reduction of intratumoral regulatory T cells (Tregs) and an increase in "M1" versus "M2" tumor-associated macrophage (TAM) phenotypes. Additionally, we observed increased immunogenic cell death as well as antigen processing in response to combination treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.