ArticleJournal for immunotherapy of cancer2022
Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- Tailored FcγR blockade enhances immune checkpoint therapy and overcomes resistance.Journal of experimental & clinical cancer research : CR · 2026Article
- Engineering antibody-armed oncolytic viruses: design strategies, synergistic mechanisms, and clinical translation.Frontiers in immunology · 2026Review
- A "Function-First" Approach to Identify Regulatory T cell-Targeting Antibodies for Immunotherapy.Cancer immunology research · 2025Article
- Vaccinia Virus-A Swiss Army Knife Against Cancer.Cancers · 2025Review
- Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies.Frontiers in immunology · 2025Review
- B cells and tertiary lymphoid structures in tumors: immunity cycle, clinical impact, and therapeutic applications.Theranostics · 2025Review
- Foxp3 inhibitory peptide encapsulated in a novel CD25-targeted nanoliposome promotes efficient tumor regression in mice.Acta pharmacologica Sinica · 2025Article
- Regulatory T cells in cancer: from immunosuppression to therapeutic targeting.Frontiers in immunology · 2025Review
- Oncolytic virus therapy in the elderly: immune frailty, challenges, and perspectives.Frontiers in immunology · 2025Review
- Overcoming resistance to PD-1 and CTLA-4 blockade mechanisms and therapeutic strategies.Frontiers in immunology · 2025Review
- Deep phenotyping of nodal T-cell lymphomas reveals immune alterations and therapeutic targets.Haematologica · 2025Article
- Quantitative Approach to Explore Regulatory T Cell Activity in Immuno-Oncology.Pharmaceutics · 2024Review
- Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.Seminars in immunopathology · 2024Review
- TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment.Journal for immunotherapy of cancer · 2024Article
- OX40L-expressing recombinant modified vaccinia virus Ankara induces potent antitumor immunity via reprogramming Tregs.The Journal of experimental medicine · 2023Article
- Both intratumoral regulatory T cell depletion and CTLA-4 antagonism are required for maximum efficacy of anti-CTLA-4 antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease.Cancer gene therapy · 2023Article
- Sequence enrichment profiles enable target-agnostic antibody generation for a broad range of antigens.Cell reports methods · 2023Article
- Review
- Oncolytic vaccinia virus and cancer immunotherapy.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint blockade (ICB) is a clinically proven concept to treat cancer. Still, a majority of patients with cancer including those with poorly immune infiltrated 'cold' tumors are resistant to currently available ICB therapies. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is one of few clinically validated targets for ICB, but toxicities linked to efficacy in approved αCTLA-4 regimens have restricted their use and precluded full therapeutic dosing. At a mechanistic level, accumulating preclinical and clinical data indicate dual mechanisms for αCTLA-4; ICB and regulatory T cell (Treg) depletion are both thought to contribute efficacy and toxicity in available, systemic, αCTLA-4 regimens. Accordingly, strategies to deliver highly effective, yet safe αCTLA-4 therapies have been lacking. Here we assess and identify spatially restricted exposure to a novel strongly Treg-depleting, checkpoint-blocking, vectorized αCTLA-4, as a highly efficacious and potentially safe strategy to target CTLA-4.
methodsA novel human IgG1 CTLA-4 antibody (4-E03) was identified using function-first screening for monoclonal antibodies (mAbs) and targets associated with superior Treg-depleting activity. A tumor-selective oncolytic vaccinia vector was then engineered to encode this novel, strongly Treg-depleting, checkpoint-blocking, αCTLA-4 antibody or a matching surrogate antibody, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (VV
resultsThe identified 4-E03 antibody showed significantly stronger Treg depletion, but equipotent checkpoint blockade, compared with clinically validated αCTLA-4 ipilimumab against CTLA-4-expressing Treg cells in a humanized mouse model in vivo. Intratumoral administration of VV
conclusionOur findings demonstrate in vivo proof of concept for spatial restriction of Treg depletion-optimized immune checkpoint blocking, vectorized αCTLA-4 as a highly effective and safe strategy to target CTLA-4. A clinical trial evaluating intratumoral VV
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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.