ArticleProceedings of the National Academy of Sciences of the United States of America2021
Targeting loss of heterozygosity for cancer-specific immunotherapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 45 papers.
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.
An Observational Study Obtaining Solid Tumor Tissue From Participants and Apheresis for CAR T-Cell Therapy Manufacturing
A Phase 1/2 Study to Evaluate the Safety and Efficacy of A2B530, an Autologous Logic-gated Tmod™ Chimeric Antigen Receptor T Cell (CAR T), in Heterozygous HLA-A*02 Adult Subjects With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression
A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Autologous Logic-gated Tmod™ CAR T Products, in Heterozygous HLA-A*02 Adults With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression
A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated Tmod™ CAR T, in Heterozygous HLA-A*02 Adults With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression
Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- Dissecting cancer in a non-mammalian model: genomic insights from lemon frost geckos.BMC biology · 2026Article
- Genomic Catastrophe Defines the Evolutionary Trajectory of Adrenocortical Carcinoma.Endocrine pathology · 2026Article
- Spatial Regulation of CAR Signaling Enables Logic-Gated Activity.bioRxiv : the preprint server for biology · 2026Article
- NOT-gated chimeric antigen receptor circuits in T and NK cells.Cell systems · 2026Article
- Article
- A method for structural variant detection using Hi-C contact matrix and neural networks.Scientific reports · 2026Article
- Targeting mutated KRAS by HLA-A*02:01 restricted anti-KRAS TCR-mimic CAR and bispecific T cell engager.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects.Journal of hematology & oncology · 2025Review
- Advances in strategies to improve the immunotherapeutic efficacy of chimeric antigen receptor-T cell therapy for lymphoma.Cancer biology & medicine · 2025Review
- Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape.eLife · 2025Article
- Multi-targeted, NOT gated CAR-T cells as a strategy to protect normal lineages for blood cancer therapy.Frontiers in immunology · 2025Article
- Article
- Review
- Review
- CD4Science immunology · 2024Article
- Detecting HLA loss of heterozygosity within a standard diagnostic sequencing workflow for prognostic and therapeutic opportunities.NPJ precision oncology · 2024Article
- Application of CAR-T cell therapy targeting mesothelin in solid tumor treatment.Discover oncology · 2024Review
- Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities.Science translational medicine · 2024Article
- Islands of genomic stability in the face of genetically unstable metastatic cancer.bioRxiv : the preprint server for biology · 2024Article
- CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity.Frontiers in immunology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Developing therapeutic agents with potent antitumor activity that spare normal tissues remains a significant challenge. Clonal loss of heterozygosity (LOH) is a widespread and irreversible genetic alteration that is exquisitely specific to cancer cells. We hypothesized that LOH events can be therapeutically targeted by "inverting" the loss of an allele in cancer cells into an activating signal. Here we describe a proof-of-concept approach utilizing engineered T cells approximating NOT-gate Boolean logic to target counterexpressed antigens resulting from LOH events in cancer. The NOT gate comprises a chimeric antigen receptor (CAR) targeting the allele of human leukocyte antigen (HLA) that is retained in the cancer cells and an inhibitory CAR (iCAR) targeting the HLA allele that is lost in the cancer cells. We demonstrate that engineered T cells incorporating such NOT-gate logic can be activated in a genetically predictable manner in vitro and in mice to kill relevant cancer cells. This therapeutic approach, termed NASCAR (Neoplasm-targeting Allele-Sensing CAR), could, in theory, be extended to LOH of other polymorphic genes that result in altered cell surface antigens in cancers.
Indexed as
Identifiers
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.