ArticleCancer immunology research2021
Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable.
Article in Cancer immunology research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Durable responses to triplet immunotherapy targeting TGF-β, PD-L1, and tumor antigen, with an IL-15 receptor superagonist in mismatch repair proficient castration-resistant prostate cancer.Journal for immunotherapy of cancer · 2026Trial
- Trial
- Perineural invasion in digestive tract tumors: Immune system interactions and therapeutic strategies.World journal of clinical oncology · 2026Review
- TIME for Endometrial Cancer: Advancements and Challenges in Therapeutic Targets for the Endometrial Cancer Tumor Immune Microenvironment.Cancer immunology research · 2025Review
- A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance.Cancer biology & therapy · 2024Review
- Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies.Cells · 2023Review
- Therapeutic challenge for immunotherapy targeting cold colorectal cancer: A narrative review.World journal of clinical oncology · 2023Review
- Exploiting the immunogenic potential of standard of care radiation or cisplatin therapy in preclinical models of HPV-associated malignancies.Journal for immunotherapy of cancer · 2022Article
- Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets.Journal of hematology & oncology · 2022Review
- Immune targeting of three independent suppressive pathways (TIGIT, PD-L1, TGFβ) provides significant antitumor efficacy in immune checkpoint resistant models.Oncoimmunology · 2022Article
- Tipping the scales: Immunotherapeutic strategies that disrupt immunosuppression and promote immune activation.Frontiers in immunology · 2022Review
- Multiple mechanisms for TRAF3-mediated regulation of the T cell costimulatory receptor GITR.The Journal of biological chemistry · 2021Article
- Vaccine Increases the Diversity and Activation of Intratumoral T Cells in the Context of Combination Immunotherapy.Cancers · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Immunotherapy of immunologically cold solid tumors may require multiple agents to engage immune effector cells, expand effector populations and activities, and enable immune responses in the tumor microenvironment (TME). To target these distinct phenomena, we strategically chose five clinical-stage immuno-oncology agents, namely, (i) a tumor antigen-targeting adenovirus-based vaccine (Ad-CEA) and an IL15 superagonist (N-803) to activate tumor-specific T cells, (ii) OX40 and GITR agonists to expand and enhance the activated effector populations, and (iii) an IDO inhibitor (IDOi) to enable effector-cell activity in the TME. Flow cytometry, T-cell receptor (TCR) sequencing, and RNA-sequencing (RNA-seq) analyses showed that in the CEA-transgenic murine colon carcinoma (MC38-CEA) tumor model, Ad-CEA + N-803 combination therapy resulted in immune-mediated antitumor effects and promoted the expression of costimulatory molecules on immune subsets, OX40 and GITR, and the inhibitory molecule IDO. Treatment with Ad-CEA + N-803 + OX40 + GITR + IDOi, termed the pentatherapy regimen, resulted in the greatest inhibition of tumor growth and protection from tumor rechallenge without toxicity. Monotherapy with any of the agents had little to no antitumor activity, whereas combining two, three, or four agents had minimal antitumor effects. Immune analyses demonstrated that the pentatherapy combination induced CD4
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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.