The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo
Open accessAbstract
The efficacy of chimeric antigen receptor (CAR) T cell therapy against poorly responding tumors can be enhanced by administering the cells in combination with immune checkpoint blockade inhibitors. Alternatively, the CAR construct has been engineered to coexpress factors that boost CAR-T cell function in the tumor microenvironment. We modified CAR-T cells to secrete PD-1-blocking single-chain variable fragments (scFv). These scFv-secreting CAR-T cells acted in both a paracrine and autocrine manner to improve the anti-tumor activity of CAR-T cells and bystander tumor-specific T cells in clinically relevant syngeneic and xenogeneic mouse models of PD-L1+ hematologic and solid tumors. The efficacy was similar to or better than that achieved by combination therapy with CAR-T cells and a checkpoint inhibitor. This approach may improve safety, as the secreted scFvs remained localized to the tumor, protecting CAR-T cells from PD-1 inhibition, which could potentially avoid toxicities associated with systemic checkpoint inhibition.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Moreover, modified CAR-T cells, which secret PD-1-blocking single-chain variable fragments (scFv), had improved antitumor activity by an autocrine and paracrine manner [345].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [345]
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
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609
In-gel digestion for mass spectrometric characterization of proteins and proteomes
Shevchenko, A., Tomas, H., Havli, J., Olsen, J. V., & Mann, M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.468 · Cited by 4,947
Rappsilber, J., Mann, M., & Ishihama, Y. (2007) · Nature Protocols · doi:10.1038/nprot.2007.261 · Cited by 4,641
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J. M., Desrichard, A., Walsh, L. A., Postow, M. A., Wong, P., Ho, T. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406498 · Cited by 4,286
Self-citationTumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089
Cited by
Sorted by citations
A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154
Engineering strategies to overcome the current roadblocks in CAR T cell therapy
Rafiq, S., Hackett, C. S., & Brentjens, R. J. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0297-y · Cited by 1,525
Self-citationCombination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445
‘Off-the-shelf’ allogeneic CAR T cells: development and challenges
Depil, S., Duchateau, P. N., Grupp, S. A., Mufti, G. J., & Poirot, L. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0051-2 · Cited by 1,266
Clinical implications of T cell exhaustion for cancer immunotherapy
Chow, A., Perica, K., Klebanoff, C. A., & Wolchok, J. D. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00689-z · Cited by 1,044
Metadata
- Authors
- Rafiq, S., Yeku, O. O., Jackson, H. J., Purdon, T. J., van Leeuwen, D. G., Drakes, D. J., Song, M., Miele, M. M., Li, Z., Wang, P., Yan, S., Xiang, J., Ma, X., Seshan, V. E., Hendrickson, R. C., Liu, C., & Brentjens, R. J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Cornell University (US)
- Weill Cornell Medicine (US)
- Eureka Therapeutics (United States) (US)
- Corresponding author
- Brentjens, Renier J
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2018-08-13
- Volume
- 36
- Issue
- 9
- Pages
- 847-856
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC6126939
- OpenAlex
- W2886131798
- Cited by
- 833
- References
- 46
- Citations by year
- 2026: 78 · 2025: 94 · 2024: 91 · 2023: 114 · 2022: 123 · 2021: 121 · 2020: 122 · 2019: 72 · 2018: 14
- FWCI
- 31.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1s10od010598-01)
- National Cancer Institute (P01CA190174, P50CA192937, P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- chimeric antigen receptor T cells, anti-PD-1 therapy, scFv, chimeric antigen receptor, immune checkpoint blockade, PD-L1, paracrine signaling, autocrine signaling, bystander T cells, tumor microenvironment, hematologic malignancies, solid tumors, CAR T cell safety
- MeSH terms
- Receptors, Chimeric Antigen, Animals, Humans, T-Lymphocytes, Xenograft Model Antitumor Assays, Mice, Single-Chain Antibodies, Tumor Microenvironment, Programmed Cell Death 1 Receptor
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
