ArticleCancer research2016
A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 328 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
328 citing papers in PubMed, 1 synthesis or guideline pooled it, 505 citations in OpenAlex.
- The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.Frontiers in immunology · 2024Pooled it
- PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Trial
- Turning immune checkpoint inhibitors into synthetic switches for engineered T cells.Molecular therapy. Oncology · 2026Article
- Novel immunotherapies for prostate cancer.Urologic oncology · 2026Review
- An inducible signal 1 booster overcomes limited access to antigen for solid tumor cell therapy.Molecular therapy. Oncology · 2026Article
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Emerging target antigen landscape for CAR T-cell therapy in solid tumors: current advances and future directions.Immunologic research · 2026Review
- Engineering Strategies for Allogeneic T Cell-Based Platforms in Cancer Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Chimeric switch scaffold protein augments CAR synapse formation and signaling networks.Journal for immunotherapy of cancer · 2026Article
- Rapidly evolved PD-1 for enhance receptor and checkpoint inhibitor in immunotherapy.Molecular therapy. Oncology · 2026Article
- T-Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan-Cancer Characteristics, and Therapeutic Interventions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TIM-3 in AML: pathogenic roles and therapeutic targetability.Clinical and experimental medicine · 2026Review
- PD-1: CD28 chimeric receptors enhance phenotypic and functional features of T cell subsets.Research in pharmaceutical sciences · 2026Article
- Dual-targeting CD133/PD-L1 CAR-T plus αPD-1 overcomes immunosuppressive microenvironment and enhanced by radiation pre-conditioning.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Integrating CAR-T therapy with PD-1/PD-L1 blockade: Mechanisms, synergy, and optimized strategies in NSCLC.iScience · 2026Review
- In Vivo CAR-T Therapies-A New Era of Programmable Immunity.International journal of molecular sciences · 2026Review
- Ibrutinib and PD-1 Blockade Potentiate Mesothelin-Targeting CAR T-cell Therapy in Preclinical Models of Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The safety and efficacy of GD2-targeted CAR-T cells in patients with neuroblastoma: a systematic review and meta-analysis.European journal of medical research · 2026Review
- Molecularly targeted therapy and immunotherapy in leukemias.Journal of hematology & oncology · 2026Review
268 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR)-modified adoptive T-cell therapy has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is the immune-suppressive effects induced in both naturally occurring and genetically modified tumor-infiltrating lymphocytes (TIL) by inhibitory receptors (IR), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR T-cell activity against solid tumors. To address this possibility, we introduced a genetically engineered switch receptor construct, comprising the truncated extracellular domain of PD1 and the transmembrane and cytoplasmic signaling domains of CD28, into CAR T cells. We tested the effect of this supplement, "PD1CD28," on human CAR T cells targeting aggressive models of human solid tumors expressing relevant tumor antigens. Treatment of mice bearing large, established solid tumors with PD1CD28 CAR T cells led to significant regression in tumor volume due to enhanced CAR TIL infiltrate, decreased susceptibility to tumor-induced hypofunction, and attenuation of IR expression compared with treatments with CAR T cells alone or PD1 antibodies. Taken together, our findings suggest that the application of PD1CD28 to boost CAR T-cell activity is efficacious against solid tumors via a variety of mechanisms, prompting clinical investigation of this potentially promising treatment modality.
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What OpenQuestion holds
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.