ArticleJournal for immunotherapy of cancer2022
Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors.
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 14 papers, 1 of them a synthesis that pooled it.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Efficacy and safety of cadonilimab for malignant solid tumor treatment: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- 3D ex vivo platform for high-throughput immunotherapy screening in relapsed/refractory lymphoma patients.HemaSphere · 2026Article
- LAG3 Gene Therapy Attenuates Autoimmune Uveitis by Regulating the PI3K/Akt Signaling Pathway.Investigative ophthalmology & visual science · 2026Article
- Innate-like T Cell Biology in the Tumor Microenvironment Implications for Cancer Immunotherapy.Cells · 2026Review
- Immunogenic clearance combined with PD-1 blockade elicits antitumor effect by promoting the recruitment and expansion of the effector memory-like CD8Translational oncology · 2025Article
- LAG-3 : recent developments in combinational therapies in cancer.Cancer science · 2024Review
- Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer.Journal of hematology & oncology · 2024Review
- An overview of statistical methods for biomarkers relevant to early clinical development of cancer immunotherapies.Frontiers in immunology · 2024Review
- Review
- Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Advances in landscape and related therapeutic targets of the prostate tumor microenvironment.Acta biochimica et biophysica Sinica · 2023Review
- Beyond CTLA-4 and PD-1 Inhibition: Novel Immune Checkpoint Molecules for Melanoma Treatment.Cancers · 2023Review
- Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy.Cancer biology & medicine · 2023Review
- The role of immunotherapy in microsatellites stable metastatic colorectal cancer: state of the art and future perspectives.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNext-generation cancer immunotherapies are designed to broaden the therapeutic repertoire by targeting new immune checkpoints including lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin and mucin-domain containing-3 (TIM-3). Yet, the molecular and cellular mechanisms by which either receptor functions to mediate its inhibitory effects are still poorly understood. Similarly, little is known on the differential effects of dual, compared with single, checkpoint inhibition.
methodsWe here performed in-depth characterization, including multicolor flow cytometry, single cell RNA sequencing and multiplex supernatant analysis, using tumor single cell suspensions from patients with cancer treated ex vivo with novel bispecific antibodies targeting programmed cell death protein 1 (PD-1) and TIM-3 (PD1-TIM3), PD-1 and LAG-3 (PD1-LAG3), or with anti-PD-1.
resultsWe identified patient samples which were responsive to PD1-TIM3, PD1-LAG3 or anti-PD-1 using an in vitro approach, validated by the analysis of 659 soluble proteins and enrichment for an anti-PD-1 responder signature. We found increased abundance of an activated (HLA-DR
conclusionsOur in vitro system reliably assessed responses to bispecific antibodies co-targeting PD-1 together with LAG-3 or TIM-3 using patients' tumor infiltrating immune cells and revealed transcriptional and phenotypic imprinting by bispecific antibody formats currently tested in early clinical trials.
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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.