Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies
Open accessPublished version of a preprint
Abstract
An engineered probiotic system locally delivers checkpoint blockade nanobodies to tumors for sustained therapeutic release.
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
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?
An E. coli Nissle 1917 strain engineered to secrete immune checkpoint blockade nanobodies and cytokines can boost antitumor responses in mouse models.
“an E. coli Nissle 1917 strain engineered to secrete immune checkpoint blockade nanobodies and cytokines can boost the antitumor responses in mouse models.176”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [176]
Gurbatri et al. engineered an Escherichia coli Nissle 1917 probiotic bacterial strain to release nanobodies targeting PD-L1 and CTLA-4 for local therapeutic activity in preclinical models.
“In 2020, Gurbatri et al. (2020) engineered an Escherichia coli Nissle 1917 probiotic bacterial strain to release nanobodies targeting PD-L1 and CTLA-4 for local therapeutic activity in preclinical models.”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Gurbatri et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
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 · cited 1× · see citing works
“While anti-PD-L1 mAbs have achieved some level of tumor regression in ~30% of cancers like melanoma (4, 5), they can also result in immune-related adverse effects (iRAEs), with up to 70% of patients experiencing a range of toxicity grades resulting in fatigue, skin rashes, endocrine disorders, or hepatic toxicities (6…”
BackgroundA synthetic oscillatory network of transcriptional regulators
Elowitz, M., & Leibler, S. (2000) · Nature · doi:10.1038/35002125 · Cited by 4,812 · see citing works
Construction of a genetic toggle switch in Escherichia coli
Gardner, T. S., Cantor, C. R., & Collins, J. J. (2000) · Nature · doi:10.1038/35002131 · Cited by 4,310 · see citing works
Immune-related adverse events with immune checkpoint blockade: a comprehensive review
Michot, J. M., Bigenwald, C., Champiat, S., Collins, M., Carbonnel, F., Postel-Vinay, S., Berdelou, A., Varga, A., Bahleda, R., Hollebecque, A., et al. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2015.11.016 · Cited by 2,127 · see citing works
Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies
Naidoo, J., Page, D. B., Li, B. T., Connell, L. C., Schindler, K., Lacouture, M. E., Postow, M. A., & Wolchok, J. D. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv383 · Cited by 1,489 · see citing works
The indigenous gastrointestinal microflora
Berg, R. (1996) · Trends in Microbiology · doi:10.1016/0966-842x(96)10057-3 · Cited by 1,153 · see citing works
A fast, robust and tunable synthetic gene oscillator
Stricker, J., Cookson, S., Bennett, M. R., Mather, W., Tsimring, L. S., & Hasty, J. (2008) · Nature · doi:10.1038/nature07389 · Cited by 1,102 · see citing works
A synchronized quorum of genetic clocks
Danino, T., Mondragón-Palomino, O., Tsimring, L. S., & Hasty, J. (2010) · Nature · doi:10.1038/nature08753 · Cited by 987 · see citing works
Self-citationFearon, E. R., Pardoll, D. M., Itaya, T., Golumbek, P. T., Levitsky, H. I., Simons, J. W., Karasuyama, H., Vogelstein, B., & Frost, P. (1990) · Cell · doi:10.1016/0092-8674(90)90591-2 · Cited by 916 · see citing works
Engineering the perfect (bacterial) cancer therapy
Forbes, N. S. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2934 · Cited by 905 · see citing works
Selby, M. J., Engelhardt, J. J., Quigley, M., Henning, K. A., Chen, T., Srinivasan, M., & Korman, A. J. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0013 · Cited by 857 · see citing works
Tumour-targeting bacteria engineered to fight cancer
Zhou, S., Gravekamp, C., Bermudes, D., & Liu, K. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0070-z · Cited by 821 · see citing works
Synchronized cycles of bacterial lysis for in vivo delivery
Din, M. O., Danino, T., Prindle, A., Skalak, M., Selimkhanov, J., Allen, K., Julio, E., Atolia, E., Tsimring, L. S., Bhatia, S. N., et al. (2016) · Nature · doi:10.1038/nature18930 · Cited by 784 · see citing works
Self-citationCD47 blockade triggers T cell–mediated destruction of immunogenic tumors
Liu, X., Pu, Y., Cron, K. R., Deng, L., Kline, J. P., Frazier, W. A., Xu, H., Peng, H., Fu, Y., & Xu, M. M. (2015) · Nature Medicine · doi:10.1038/nm.3931 · Cited by 770 · see citing works
Kim, K., Skora, A. D., Li, Z., Liu, Q., Tam, A. J., Blosser, R. L., Diaz, L. A., Papadopoulos, N., Kinzler, K. W., Vogelstein, B., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410626111 · Cited by 676 · see citing works
D’Angelo, S. P., Larkin, J., Sosman, J. A., Lebbé, C., Brady, B., Neyns, B., Schmidt, H., Hassel, J. C., Hodi, F. S., Lorigan, P. C., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.9258 · Cited by 653 · see citing works
Zheng, J. H., Nguyen, V. H., Jiang, S.-N., Park, S.-H., Tan, W., Hong, S. H., Shin, M. G., Chung, I.-J., Hong, Y., Bom, H.-S., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aak9537 · Cited by 588 · see citing works
Haldimann, A., & Wanner, B. L. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.21.6384-6393.2001 · Cited by 578 · see citing works
Environmentally Controlled Invasion of Cancer Cells by Engineered Bacteria
Anderson, J. C., Clarke, E. J., Arkin, A. P., & Voigt, C. A. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.10.076 · Cited by 572 · see citing works
Nanobodies and nanobody-based human heavy chain antibodies as antitumor therapeutics
Bannas, P., Hambach, J., & Koch-Nolte, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01603 · Cited by 572 · see citing works
on behalf of the Intensive Care in Hematological and Oncological Patients (iCHOP) Collaborative Group, Kroschinsky, F., Stölzel, F., von Bonin, S., Beutel, G., Kochanek, M., Kiehl, M. G., & Schellongowski, P. (2017) · Critical Care · doi:10.1186/s13054-017-1678-1 · Cited by 505 · see citing works
Zhao, M. D., Yang, M., Li, X., Jiang, P., Baranov, E., Li, S., Xu, M., Penman, S., & Hoffman, R. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408422102 · Cited by 488 · see citing works
A Synthetic Genetic Edge Detection Program
Tabor, J. J., Salis, H. M., Simpson, Z. B., Chevalier, A. A., Levskaya, A., Marcotte, E. M., Voigt, C. A., & Ellington, A. D. (2009) · Cell · doi:10.1016/j.cell.2009.04.048 · Cited by 485 · see citing works
Programmable probiotics for detection of cancer in urine
Danino, T., Prindle, A. B., Kwong, G. A., Skalak, M., Li, H. Y., Allen, K. N., Hasty, J., & Bhatia, S. N. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa3519 · Cited by 472 · see citing works
Self-citationHwang, I. Y., Koh, E., Wong, A., March, J. C., Bentley, W. E., Lee, Y. S., & Chang, M. W. (2017) · Nature Communications · doi:10.1038/ncomms15028 · Cited by 472 · see citing works
Sequential Establishment of Stripe Patterns in an Expanding Cell Population
Liu, C., Fu, X., Liu, L., Ren, X., Chau, C. K., Li, S., Lu, X., Zeng, H., Chen, G., Tang, L., et al. (2011) · Science · doi:10.1126/science.1209042 · Cited by 453 · see citing works
Chae, Y. K., Arya, A., Iams, W. T., Cruz, M. R. D. S., Chandra, S., Choi, J., & Giles, F. J. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0349-3 · Cited by 450 · see citing works
Sagiv-Barfi, I., Kohrt, H. E. K., Czerwinski, D. K., Ng, P. P., Chang, B. Y., & Levy, R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1500712112 · Cited by 441 · see citing works
A sensing array of radically coupled genetic ‘biopixels’
Prindle, A. B., Samayoa, P., Razinkov, I., Danino, T., Tsimring, L. S., & Hasty, J. (2011) · Nature · doi:10.1038/nature10722 · Cited by 390 · see citing works
Self-citationIpilimumab Plus Sargramostim vs Ipilimumab Alone for Treatment of Metastatic Melanoma
Hodi, F. S., Lee, S., McDermott, D. F., Rao, U. N. M., Butterfield, L. H., Tarhini, A. A., Leming, P. D., Puzanov, I. J., Shin, D., & Kirkwood, J. M. (2014) · JAMA · doi:10.1001/jama.2014.13943 · Cited by 358 · see citing works
Leschner, S., Westphal, K., Dietrich, N. L., Viegas, N., Jabłońska, J., Łyszkiewicz, M., Lienenklaus, S., Falk, W., Gekara, N. O., Loessner, H., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006692 · Cited by 238 · see citing works
Lian, H., Yang, H., Tang, J., Liu, Z., Chen, Y., Lu, B., He, H., Tang, S., Sun, Y., Liu, F., et al. (2019) · Journal of Biological Engineering · doi:10.1186/s13036-019-0189-9 · Cited by 212 · see citing works
Lussier, D. M., Johnson, J. L., Hingorani, P., & Blattman, J. N. (2015) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-015-0067-z · Cited by 206 · see citing works
Rios‐Doria, J., Durham, N. M., Wetzel, L. K., Rothstein, R. P., Chesebrough, J. W., Holoweckyj, N., Zhao, W., Leow, C. C., & Hollingsworth, R. E. (2015) · Neoplasia · doi:10.1016/j.neo.2015.08.004 · Cited by 174 · see citing works
Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy
Hu, Y., Liu, C., & Muyldermans, S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01442 · Cited by 171 · see citing works
Redmond, W. L., Linch, S. N., & Kasiewicz, M. J. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0031-t · Cited by 168 · see citing works
Sécher, T., Kassem, S., Benamar, M., Bernard, I., Boury, M., Barreau, F., Oswald, É., & Saoudi, A. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01096 · Cited by 148 · see citing works
Therapy of advanced prostate cancer with granulocyte macrophage colony-stimulating factor.
Small, E. J., Reese, D., Um, B., Whisenant, S. P., Dixon, S. C., & Figg, W. D. (1999) · PubMed · Cited by 145 · see citing works
Zhang, Y., Zhang, Y., Xia, L., Zhang, X., Ding, X., Yan, F., & Wu, F. (2012) · Applied and Environmental Microbiology · doi:10.1128/aem.01390-12 · Cited by 138 · see citing works
Du, X., Liu, M., Su, J., Zhang, P., Tang, F., Ye, P., Devenport, M., Wang, X., Zhang, Y., Liu, Y., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0012-z · Cited by 123 · see citing works
Zhang, T., Xie, J., Arai, S., Wang, L., Shi, X., Shi, N., Ma, F., Chen, S., Huang, L. J., Yang, L., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.12230 · Cited by 95 · see citing works
New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness
Corraliza-Gorjón, I., Somovilla-Crespo, B., Santamaría, S. S., García‐Sanz, J. A., & Kremer, L. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01804 · Cited by 68 · see citing works
Challenges to production of antibodies in bacteria and yeast
Lee, Y. J., & Jeong, K. J. (2015) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2015.03.009 · Cited by 67 · see citing works
In Vivo Gene Expression Dynamics of Tumor-Targeted Bacteria
Danino, T., Lo, J. H.-J., Prindle, A. B., Hasty, J., & Bhatia, S. N. (2012) · ACS Synthetic Biology · doi:10.1021/sb3000639 · Cited by 62 · see citing works
Self-citationDeveloping combination strategies using PD-1 checkpoint inhibitors to treat cancer
Schmidt, E. V. (2018) · Seminars in Immunopathology · doi:10.1007/s00281-018-0714-9 · Cited by 62 · see citing works
Fedorec, A. J. H., Ozdemir, T., Doshi, A., Ho, Y.-K., Rosa, L., Rutter, J. W., Velazquez, O. S., Pinheiro, V. B., Danino, T., & Barnes, C. P. (2019) · iScience · doi:10.1016/j.isci.2019.03.019 · Cited by 57 · see citing works
Self-citationBacterial variability in the mammalian gut captured by a single-cell synthetic oscillator
Riglar, D. T., Richmond, D., Potvin-Trottier, L., Verdegaal, A. A., Naydich, A. D., Bakshi, S., Leoncini, E., Lyon, L. G., Paulsson, J., & Silver, P. A. (2019) · Nature Communications · doi:10.1038/s41467-019-12638-z · Cited by 50 · see citing works
Wu, F. T. H., Xu, P., Chow, A., Man, S., Krüger, J., Khan, K. A., Paez-Ribes, M., Pham, E., & Kerbel, R. S. (2019) · British Journal of Cancer · doi:10.1038/s41416-018-0297-1 · Cited by 47 · see citing works
Savage, D. C. (1987) · Food / Nahrung · doi:10.1002/food.19870310511 · Cited by 37 · see citing works
Estimating the Instability Parameters of Plasmid-Bearing Cells. I. Chemostat Culture
Ganusov, V. V., & Brilkov, A. V. (2002) · Journal of Theoretical Biology · doi:10.1006/jtbi.2002.3101 · Cited by 28 · see citing works
Kim, K., Skora, A. D., Li, Z., et al. (2014) · Journal for ImmunoTherapy of Cancer · doi:10.1186/2051-1426-2-s3-p267 · Cited by 27 · see citing works
Everly, J. J., & Lonial, S. (2005) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.5.3.293 · Cited by 23 · see citing works
Boe, L. (1996) · Plasmid · doi:10.1006/plas.1996.0043 · Cited by 16 · see citing works
Sandage, B. W., Talley, J. J., Martinez, E. J., et al. (2017) · Cancer Research · doi:10.1158/1538-7445.am2017-2619 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The microbiome and human cancer
Sepich-Poore, G. D., Zitvogel, L., Straussman, R., Hasty, J., Wargo, J. A., & Knight, R. (2021) · Science · doi:10.1126/science.abc4552 · Cited by 1,332 · see citing works
Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity
Leventhal, D. S., Sokolovska, A., Li, N., Plescia, C., Kolodziej, S. A., Gallant, C. W., Christmas, R., Gao, J.-R., James, M. J., Abin-Fuentes, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16602-0 · Cited by 458 · see citing works
The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored
Chandra, S., Sisodia, S. S., & Vassar, R. J. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00595-7 · Cited by 278 · see citing works
Probiotic-guided CAR-T cells for solid tumor targeting
Vincent, R. L., Gurbatri, C. R., Li, F., Vardoshvili, A., Coker, C., Im, J., Ballister, E. R., Rouanne, M., Savage, T., de los Santos-Alexis, K., et al. (2023) · Science · doi:10.1126/science.add7034 · Cited by 273 · see citing works
Self-citationMelanoma and microbiota: Current understanding and future directions
Routy, B., Jackson, T., Mählmann, L., Baumgartner, C. K., Blaser, M., Byrd, A., Corvaia, N., Couts, K., Davar, D., Derosa, L., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2023.12.003 · Cited by 89 · see citing works
Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy
Davar, D., & Zarour, H. M. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1129 · Cited by 40 · see citing works
Microbiota-centered interventions to boost immune checkpoint blockade therapies
Almonte, A. A., Thomas, S., & Zitvogel, L. (2025) · Journal of Experimental Medicine · doi:10.1084/jem.20250378 · Cited by 19 · see citing works
- Authors
- Gurbatri, C. R., Lia, I., Vincent, R., Coker, C., Castro, S., Treuting, P. M., Hinchliffe, T. E., Arpaia, N., & Danino, T.
- Affiliations
- Columbia University (US)
- University of Washington (US)
- Herbert Irving Comprehensive Cancer Center (US)
- Corresponding author
- Danino, Tal
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2020-02-12
- Volume
- 12
- Issue
- 530
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC7685004
- OpenAlex
- W3005566802
- Cited by
- 647
- References
- 55
- Citations by year
- 2026: 130 · 2025: 140 · 2024: 123 · 2023: 99 · 2022: 62 · 2021: 64 · 2020: 25 · 2019: 2 · 2012: 1
- FWCI
- 32.31
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science Translational Medicine (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (1644869)
- U.S. Department of Defense (LC160314, BC160541)
- NIH Office of the Director (R00CA197649-02)
- Breast Cancer Research Foundation (PC 516160)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- engineered probiotics, anticancer drug delivery, immune checkpoint inhibitors, nanobodies, PD-L1, CTLA-4, synthetic biology, abscopal effect, T cell memory, GM-CSF, cancer immunotherapy, syngeneic mouse model
- MeSH terms
- Animals, Disease Models, Animal, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Probiotics, Mice, CTLA-4 Antigen, Single-Domain Antibodies
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
