ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Combined CD28 and 4-1BB Costimulation Potentiates Affinity-tuned Chimeric Antigen Receptor-engineered T Cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
What it found
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Who cites it
123 citing papers in PubMed, 173 citations in OpenAlex.
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- Antigen-IL-2 CAR-enhancer drives CAR-T fate and stemness, enhancing antitumor efficacy across models independent of IL-2Rα.Journal for immunotherapy of cancer · 2026Article
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Systematic optimization of PD-L1 and CLDN18.2 CAR-T designs identifies a bicistronic dual-target, double-CD3ζ architecture with enhanced antitumor activity in gastric cancer.Frontiers in immunology · 2026Article
- Advanced strategies to enhance the safety, persistence, and efficacy of CAR-T cells in solid tumors.Frontiers in immunology · 2026Review
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- Revisiting the Ofatumumab Epitope on CD20 through Integrative Molecular Dynamics and Flow Cytometry Analyses.Computational and structural biotechnology journal · 2026Article
- Advancements and expanding applications of CAR-T cell therapy.Frontiers in immunology · 2026Review
- Targeting CAR-T cell exhaustion in non-Hodgkin lymphoma: mechanistic insights and emerging clinical strategies.Frontiers in immunology · 2026Review
- Advancing breast cancer treatment through dual targeting CAR T cell therapy.Discover oncology · 2025Review
- Review
- Generating potent and persistent antitumor immunity via affinity-tuned CAR-T cells targeting mesothelin.Acta pharmacologica Sinica · 2025Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
purposeTargeting nonspecific, tumor-associated antigens (TAA) with chimeric antigen receptors (CAR) requires specific attention to restrict possible detrimental on-target/off-tumor effects. A reduced affinity may direct CAR-engineered T (CAR-T) cells to tumor cells expressing high TAA levels while sparing low expressing normal tissues. However, decreasing the affinity of the CAR-target binding may compromise the overall antitumor effects. Here, we demonstrate the prime importance of the type of intracellular signaling on the function of low-affinity CAR-T cells. EXPERIMENTAL
designWe used a series of single-chain variable fragments (scFv) with five different affinities targeting the same epitope of the multiple myeloma-associated CD38 antigen. The scFvs were incorporated in three different CAR costimulation designs and we evaluated the antitumor functionality and off-tumor toxicity of the generated CAR-T cells
resultsWe show that the inferior cytotoxicity and cytokine secretion mediated by CD38 CARs of very low-affinity (
conclusionsA combinatorial costimulatory design allows the use of very low-affinity binding domains (
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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.