ArticleCancer research2014
SA-4-1BBL and monophosphoryl lipid A constitute an efficacious combination adjuvant for cancer vaccines.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Elucidating the Mechanisms of SA-4-1BBL-Mediated Cancer Immunoprevention Through Advanced Informatics Approaches.Biomolecules · 2026Article
- Immunoprevention of non-viral cancers: challenges and strategies for early intervention.Cancer cell international · 2025Review
- The implication of dendritic cells in lung diseases: Immunological role of toll-like receptor 4.Genes & diseases · 2024Review
- Long-term antigen-specific immune response by an oncolytic adenovirus encoding SP-SA-E7-4-1BBL in HPV-16 cancer model.Molecular biology reports · 2024Article
- A novel agonist of 4-1BB costimulatory receptor shows therapeutic efficacy against a tobacco carcinogen-induced lung cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Engineering pancreatic islets with a novel form of thrombomodulin protein to overcome early graft loss triggered by instant blood-mediated inflammatory reaction.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Article
- Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications.Frontiers in immunology · 2023Review
- CD137 Costimulation Enhances the Antitumor Activity of Vγ9Vδ2-T Cells in IL-10-Mediated Immunosuppressive Tumor Microenvironment.Frontiers in immunology · 2022Article
- 4-1BBL as a Mediator of Cross-Talk between Innate, Adaptive, and Regulatory Immunity against Cancer.International journal of molecular sciences · 2021Review
- Remission-Stage Ovarian Cancer Cell Vaccine with Cowpea Mosaic Virus Adjuvant Prevents Tumor Growth.Cancers · 2021Article
- Delivery of the RadionuclideInternational journal of molecular sciences · 2021Article
- CD137 costimulation enhances the antiviral activity of Vγ9Vδ2-T cells against influenza virus.Signal transduction and targeted therapy · 2020Article
- Recombinant Costimulatory Fusion Proteins as Functional Immunomodulators Enhance Antitumor Activity in Murine B16F10 Melanoma.Vaccines · 2020Article
- Insights of Novel Coronavirus (SARS-CoV-2) disease outbreak, management and treatment.AIMS microbiology · 2020Review
- Article
- The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans.Viruses · 2019Review
- A Novel Form of 4-1BBL Prevents Cancer Development via Nonspecific Activation of CD4Cancer research · 2019Article
- Current challenges for cancer vaccine adjuvant development.Expert review of vaccines · 2018Review
- Current perspectives of SA-4-1BBL in immune modulation during cancer.Experimental and therapeutic medicine · 2018Article
- Hsp90 Inhibition Reduces TLR5 Surface Expression and NF-BioMed research international · 2018Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Vaccines based on tumor-associated antigens (TAA) have limited therapeutic efficacy due to their weak immunogenic nature and the various immune evasion mechanisms active in advanced tumors. In an effort to overcome these limitations, we evaluated a combination of the T-cell costimulatory molecule SA-4-1BBL with the TLR4 agonist monophosphoryl lipid A (MPL) as a novel vaccine adjuvant system. In the TC-1 mouse allograft model of human papilloma virus (HPV)-induced cancer, a single administration of this combination adjuvant with HPV E7 protein caused tumor rejection in all tumor-bearing mice. On its own, SA-4-1BBL outperformed MPL in this setting. Against established tumors, two vaccinations were sufficient to elicit rejection in the majority of mice. In the metastatic model of Lewis lung carcinoma, vaccination of the TAA survivin with SA-4-1BBL/MPL yielded superior efficacy against pulmonary metastases. Therapeutic efficacy of SA-4-1BBL/MPL was achieved in the absence of detectable toxicity, correlating with enhanced dendritic cell activation, CD8(+) T-cell function, and an increased intratumoral ratio of CD8(+) T effector cells to CD4(+)FoxP3(+) T regulatory cells. Unexpectedly, use of MPL on its own was associated with unfavorable intratumoral ratios of these T-cell populations, resulting in suboptimal efficacy. The efficacy of MPL monotherapy was restored by depletion of T regulatory cells, whereas eliminating CD8(+) T cells abolished the efficacy of its combination with SA-4-1BBL. Mechanistic investigations showed that IFNγ played a critical role in supporting the therapeutic effect of SA-4-1BBL/MPL. Taken together, our results offer a preclinical proof of concept for the use of a powerful new adjuvant system for TAA-based cancer vaccines.
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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.