The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation
Open accessAbstract
Successful tumor eradication by chimeric antigen receptor-expressing (CAR-expressing) T lymphocytes depends on CAR T cell persistence and effector function. We hypothesized that CD4+ and CD8+ T cells may exhibit distinct persistence and effector phenotypes, depending on the identity of specific intracellular signaling domains (ICDs) used to generate the CAR. First, we demonstrate that the ICOS ICD dramatically enhanced the in vivo persistence of CAR-expressing CD4+ T cells that, in turn, increased the persistence of CD8+ T cells expressing either CD28- or 4-1BB-based CARs. These data indicate that persistence of CD8+ T cells was highly dependent on a helper effect provided by the ICD used to redirect CD4+ T cells. Second, we discovered that combining ICOS and 4-1BB ICDs in a third-generation CAR displayed superior antitumor effects and increased persistence in vivo. Interestingly, we found that the membrane-proximal ICD displayed a dominant effect over the distal domain in third-generation CARs. The optimal antitumor and persistence benefits observed in third-generation ICOSBBz CAR T cells required the ICOS ICD to be positioned proximal to the cell membrane and linked to the ICOS transmembrane domain. Thus, CARs with ICOS and 4-1BB ICD demonstrate increased efficacy in solid tumor models over our current 4-1BB-based CAR and are promising therapeutics for clinical testing.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407222 · Cited by 5,413
Self-citationChimeric antigen receptor–modified T cells in chronic lymphoid leukemia
Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103849 · Cited by 3,565
Self-citationChimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509
Self-citationCancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes
Dudley, M. E., Wunderlich, J. R., Robbins, P. F., Yang, J. C., Hwu, P., Schwartzentruber, D. J., Topalian, S. L., Sherry, R., Restifo, N. P., Hubicki, A. M., et al. (2002) · Science · doi:10.1126/science.1076514 · Cited by 2,823
Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia
Davila, M. L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., Chung, S. S., Stefanski, J., Borquez-Ojeda, O., Olszewska, M., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008226 · Cited by 2,476
CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
Turtle, C. J., Hanafi, L.-A., Berger, C., Gooley, T. A., Cherian, S., Hudecek, M., Sommermeyer, D., Melville, K., Pender, B., Budiarto, T. M., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85309 · Cited by 2,112
Brentjens, R. J., Davila, M. L., Riviere, I., Park, J., Wang, X., Cowell, L. G., Bartido, S., Stefanski, J., Taylor, C., Olszewska, M., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005930 · Cited by 2,063
A human memory T cell subset with stem cell–like properties
Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C. M., Quigley, M. F., Almeida, J. R., Gostick, E., Yu, Z., Carpenito, C., et al. (2011) · Nature Medicine · doi:10.1038/nm.2446 · Cited by 1,974 · cited 1×
“However, preclinical studies indicate that some T cell subtypes show distinct properties in vivo, such as enhanced proliferative capacity and increased antitumor effects (16, 17).”
BackgroundSelf-citationTargeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
Eyquem, J., Mansilla-Soto, J., Giavridis, T., van der Stegen, S. J. C., Hamieh, M., Cunanan, K. M., Odak, A., Gönen, M., & Sadelain, M. (2017) · Nature · doi:10.1038/nature21405 · Cited by 1,831 · cited 1×
“use of the 4-1BB ICD (25), optimization of the spacer length (50), targeting of a CAR to the T cell receptor α constant TRAC locus (52), or use of self-inactivating LVs instead of gammaretroviral vectors (51).”
MethodLong, A. H., Haso, W. M., Shern, J. F., Wanhainen, K. M., Murgai, M., Ingaramo, M., Smith, J. P., Walker, A. J., Kohler, M. E., Venkateshwara, V. R., et al. (2015) · Nature Medicine · doi:10.1038/nm.3838 · Cited by 1,815
Cited by
CAR-T cell therapy: current limitations and potential strategies
Sterner, R. C., & Sterner, R. M. (2021) · Blood Cancer Journal · doi:10.1038/s41408-021-00459-7 · Cited by 2,926
Recent advances and discoveries in the mechanisms and functions of CAR T cells
Larson, R. C., & Maus, M. V. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-020-00323-z · Cited by 852
CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?
Wagner, J., Wickman, E., DeRenzo, C., & Gottschalk, S. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.09.015 · Cited by 380
Vitanza, N. A., Wilson, A. L., Huang, W., Seidel, K., Brown, C., Gustafson, J. A., Yokoyama, J. K., Johnson, A. J., Baxter, B. A., Koning, R. W., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0750 · Cited by 279
CAR-T cell performance: How to improve their persistence?
López-Cantillo, G., Urueña, C., Camacho, B. A., & Ramírez-Segura, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.878209 · Cited by 207
Metadata
- Authors
- Guedan, S., Posey, A. D., Shaw, C., Wing, A., Da, T., Patel, P. R., McGettigan, S. E., Casado-Medrano, V., Kawalekar, O. U., Uribe-Herranz, M., Song, D., Melenhorst, J. J., Lacey, S. F., Scholler, J., Keith, B., Young, R. M., & June, C. H.
- Venue
- JCI Insight
- Published
- 2018-01-11
- Volume
- 3
- Issue
- 1
- ISSN
- 2379-3708 (ISSN-L)
- OpenAlex
- W2783304290
- Cited by
- 580
- References
- 58
- FWCI
- 21.49
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation. https://app.cochat.ai/papers/10.1172/jci.insight.96976
- The paper
- Guedan, S., Posey, A. D., Shaw, C., Wing, A., Da, T., Patel, P. R., McGettigan, S. E., Casado-Medrano, V., Kawalekar, O. U., Uribe-Herranz, M., Song, D., Melenhorst, J. J., Lacey, S. F., Scholler, J., Keith, B., Young, R. M., & June, C. H. (2018). Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation. JCI Insight. https://doi.org/10.1172/jci.insight.96976
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
