Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities

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

Microenvironmental regulation of tumor progression and metastasis

Quail, D. F., & Joyce, J. A. (2013) · Nature Medicine · doi:10.1038/nm.3394 · Cited by 7,994

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

Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment

Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632

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

Chimeric 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

Molecular mechanisms of T cell co-stimulation and co-inhibition

Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial

Lee, D. W., Kochenderfer, J. N., Stetler-Stevenson, M., Cui, Y. K., Delbrook, C., Feldman, S. A., Fry, T. J., Orentas, R., Sabatino, M., Shah, N. N., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61403-3 · Cited by 2,898

Notch signalling: a simple pathway becomes complex

Bray, S. J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2009 · Cited by 2,620

Cancer regression in patients after transfer of genetically engineered lymphocytes

Morgan, R. A., Dudley, M. E., Wunderlich, J. R., Hughes, M. S., Yang, J. C., Sherry, R. M., Royal, R. E., Topalian, S. L., Kammula, U. S., Restifo, N. P., et al. (2006) · Science · doi:10.1126/science.1129003 · Cited by 2,603

T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia

Kalos, M. D., Levine, B. L., Porter, D. L., Katz, S. I., Grupp, S. A., Bagg, A., & June, C. H. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002842 · Cited by 2,417

Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential

Sharma, P., & Allison, J. P. (2015) · Cell · doi:10.1016/j.cell.2015.03.030 · Cited by 2,345

Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer Immunotherapy

Rosenberg, S. A., Yang, J. C., Sherry, R. M., Kammula, U. S., Hughes, M. S., Phan, G. Q., Citrin, D. E., Restifo, N. P., Robbins, P. F., Wunderlich, J. R., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0116 · Cited by 2,208

Cancer immunotherapy via dendritic cells

Palucka, K., & Banchereau, J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3258 · Cited by 2,114

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia

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

The microbiome and innate immunity

Thaiss, C. A., Zmora, N., Levy, M., & Elinav, E. (2016) · Nature · doi:10.1038/nature18847 · Cited by 2,012

Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia

Porter, D. L., Hwang, W.-T., Frey, N. V., Lacey, S. F., Shaw, P. A., Loren, A. W., Bagg, A., Marcucci, K. T., Shen, A., Gonzalez, V., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac5415 · Cited by 1,729

Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors.

Eshhar, Z., Waks, T., Gross, G., & Schindler, D. G. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.720 · Cited by 1,668

Up on the tightrope: natural killer cell activation and inhibition

Lanier, L. L. (2008) · Nature Immunology · doi:10.1038/ni1581 · Cited by 1,656

Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1

Robbins, P. F., Morgan, R. A., Feldman, S. A., Yang, J. C.-H., Sherry, R. M., Dudley, M. E., Wunderlich, J. R., Nahvi, A. V., Helman, L. J., Mackall, C. L., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.2537 · Cited by 1,635

Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain

Schroeter, E. H., Kisslinger, J. A., & Kopan, R. (1998) · Nature · doi:10.1038/30756 · Cited by 1,624

Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity.

Gross, G., Waks, T., & Eshhar, Z. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.24.10024 · Cited by 1,597

The Basic Principles of Chimeric Antigen Receptor Design

Sadelain, M., Brentjens, R. J., & Rivière, I. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0548 · Cited by 1,597

Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor

Kochenderfer, J. N., Dudley, M. E., Kassim, S. H., Somerville, R. P. T., Carpenter, R. O., Stetler-Stevenson, M., Yang, J. C., Phan, G. Q., Hughes, M. S., Sherry, R. M., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.56.2025 · Cited by 1,595

Inducible Apoptosis as a Safety Switch for Adoptive Cell Therapy

Di Stasi, A., Tey, S.-K., Dotti, G., Fujita, Y., Kennedy-Nasser, A., Martinez, C., Straathof, K., Liu, E., Durett, A. G., Grilley, B., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1106152 · Cited by 1,512

B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cells

Kochenderfer, J. N., Dudley, M. E., Feldman, S. A., Wilson, W. H., Spaner, D., Marić, I., Stetler‐Stevenson, M., Phan, G. Q., Hughes, M. S., Sherry, R. M., et al. (2011) · Blood · doi:10.1182/blood-2011-10-384388 · Cited by 1,454

Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen

Johnson, L. A., Morgan, R. A., Dudley, M. E., Cassard, L., Yang, J. C.-H., Hughes, M. S., Kammula, U. S., Royal, R. E., Sherry, R. M., Wunderlich, J. R., et al. (2009) · Blood · doi:10.1182/blood-2009-03-211714 · Cited by 1,421

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19

Kochenderfer, J. N., Wilson, W. H., Janik, J. E., Dudley, M. E., Stetler-Stevenson, M., Feldman, S. A., Maric, I., Raffeld, M., Nathan, D.-A. N., Lanier, B. J., et al. (2010) · Blood · doi:10.1182/blood-2010-04-281931 · Cited by 1,337

Adoptive Cell Therapy for Patients With Metastatic Melanoma: Evaluation of Intensive Myeloablative Chemoradiation Preparative Regimens

Dudley, M. E., Yang, J. C., Sherry, R. M., Hughes, M. S., Royal, R. E., Kammula, U. S., Robbins, P. F., Huang, J., Citrin, D. E., Leitman, S. F., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.5449 · Cited by 1,334

Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias

Brentjens, R. J., Rivière, I., Park, J. H., Davila, M. L., Wang, X., Stefanski, J., Taylor, C., Yeh, R., Bartido, S. M., Bórquez-Ojeda, O., et al. (2011) · Blood · doi:10.1182/blood-2011-04-348540 · Cited by 1,293

Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells

Kawalekar, O. U., O’Connor, R. S., Fraietta, J. A., Guo, L., McGettigan, S. E., Posey, A. D., Patel, P. R., Guedan, S., Scholler, J., Keith, B., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.021 · Cited by 1,267

Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma

Linette, G. P., Stadtmauer, E. A., Maus, M. V., Rapoport, A. P., Levine, B. L., Emery, L., Litzky, L. A., Bagg, A., Carreno, B. M., Cimino, P. J., et al. (2013) · Blood · doi:10.1182/blood-2013-03-490565 · Cited by 1,209

Chimeric Receptors Containing CD137 Signal Transduction Domains Mediate Enhanced Survival of T Cells and Increased Antileukemic Efficacy In Vivo

Milone, M. C., Fish, J. D., Carpenito, C., Carroll, R. G., Binder, G. K., Teachey, D., Samanta, M., Lakhal, M., Gloss, B., Danet-Desnoyers, G., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.83 · Cited by 1,197

Cancer Regression and Neurological Toxicity Following Anti-MAGE-A3 TCR Gene Therapy

Morgan, R. A., Chinnasamy, N., Abate‐Daga, D., Gros, A., Robbins, P. F., Zheng, Z., Dudley, M. E., Feldman, S. A., Yang, J. C., Sherry, R. M., et al. (2013) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3182829903 · Cited by 1,181

HSV-TK Gene Transfer into Donor Lymphocytes for Control of Allogeneic Graft-Versus-Leukemia

Bonini, C., Ferrari, G., Verzeletti, S., Servida, P., Zappone, E., Ruggieri, L., Ponzoni, M., Rossini, S., Mavilio, F., Traversari, C., et al. (1997) · Science · doi:10.1126/science.276.5319.1719 · Cited by 1,158

Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRζ /CD28 receptor

Maher, J. F., Brentjens, R. J., Gunset, G., Rivière, I., & Sadelain, M. (2002) · Nature Biotechnology · doi:10.1038/nbt0102-70 · Cited by 1,062

Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits

Roybal, K. T., Rupp, L. J., Morsut, L., Walker, W. J., McNally, K. A., Park, J. S., & Lim, W. A. (2016) · Cell · doi:10.1016/j.cell.2016.01.011 · Cited by 1,033

T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of Metastatic Colorectal Cancer but Induce Severe Transient Colitis

Parkhurst, M. R., Yang, J. C.-H., Langan, R. C., Dudley, M. E., Nathan, D.-A. N., Feldman, S. A., Davis, J. L., Morgan, R. A., Merino, M. J., Sherry, R. M., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.272 · Cited by 1,025

Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors

Morsut, L., Roybal, K. T., Xiong, X., Gordley, R. M., Coyle, S. M., Thomson, M., & Lim, W. A. (2016) · Cell · doi:10.1016/j.cell.2016.01.012 · Cited by 1,019

Coinhibitory Pathways in Immunotherapy for Cancer

Baumeister, S. H. C., Freeman, G. J., Dranoff, G., & Sharpe, A. H. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112049 · Cited by 937

Dendritic Cells Prime Natural Killer Cells by trans-Presenting Interleukin 15

Lucas, M., Schachterle, W., Oberle, K., Aichele, P., & Diefenbach, A. (2007) · Immunity · doi:10.1016/j.immuni.2007.03.006 · Cited by 888

NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma

Rapoport, A. P., Stadtmauer, E. A., Binder-Scholl, G. K., Goloubeva, O. G., Vogl, D. T., Lacey, S. F., Badros, A. Z., Garfall, A. L., Weiss, B. M., Finklestein, J. M., et al. (2015) · Nature Medicine · doi:10.1038/nm.3910 · Cited by 884

Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells

Kloss, C. C., Condomines, M., Cartellieri, M., Bachmann, M. P., & Sadelain, M. (2012) · Nature Biotechnology · doi:10.1038/nbt.2459 · Cited by 860

Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes

Caruana, I., Savoldo, B., Hoyos, V., Weber, G., Liu, H., Kim, E. S., Ittmann, M., Marchetti, D., & Dotti, G. (2015) · Nature Medicine · doi:10.1038/nm.3833 · Cited by 844

Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production.

Leonard, J. P., Sherman, M. L., Fisher, G. L., Buchanan, L. J., Larsen, G., Atkins, M. B., Sosman, J. A., Dutcher, J. P., Vogelzang, N. J., & Ryan, J. L. (1997) · PubMed · Cited by 820

Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells

Gallina, G., Dolcetti, L., Serafini, P., Santo, C. D., Marigo, I., Colombo, M. P., Basso, G., Brombacher, F., Borrello, I., Zanovello, P., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28828 · Cited by 807

The cytoplasmic domain of the T cell receptor ζ chain is sufficient to couple to receptor-associated signal transduction pathways

Irving, B. A., & Weiss, A. (1991) · Cell · doi:10.1016/0092-8674(91)90314-o · Cited by 806

PD-1– and CTLA-4–Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses

Fedorov, V. D., Themeli, M., & Sadelain, M. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006597 · Cited by 752

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

Ellebrecht, C. T., Bhoj, V. G., Nace, A., Choi, E. J., Mao, X., Cho, M. J., Zenzo, G. D., Lanzavecchia, A., Seykora, J. T., Cotsarelis, G., et al. (2016) · Science · doi:10.1126/science.aaf6756 · Cited by 751

Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors

Roybal, K. T., Williams, J. Z., Morsut, L., Rupp, L. J., Kolinko, I., Choe, J. H., Walker, W. J., McNally, K. A., & Lim, W. A. (2016) · Cell · doi:10.1016/j.cell.2016.09.011 · Cited by 731

Remote control of therapeutic T cells through a small molecule–gated chimeric receptor

Wu, C.-Y., Roybal, K. T., Puchner, E. M., Onuffer, J., & Lim, W. A. (2015) · Science · doi:10.1126/science.aab4077 · Cited by 706

Stress, Inflammation, and Defense of Homeostasis

Chovatiya, R., & Medzhitov, R. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.030 · Cited by 704

Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning

Pegram, H. J., Lee, J., Hayman, E. G., Imperato, G. H., Tedder, T. F., Sadelain, M., & Brentjens, R. J. (2012) · Blood · doi:10.1182/blood-2011-12-400044 · Cited by 686

Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells

Imai, C., Iwamoto, S., & Campana, D. (2005) · Blood · doi:10.1182/blood-2004-12-4797 · Cited by 661

Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T Cells

Scholler, J., Brady, T., Binder-Scholl, G. K., Hwang, W., Plesa, G., Hege, K. M., Vogel, A. N., Kalos, M. D., Riley, J. L., Deeks, S. G., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003761 · Cited by 654

N OTCH AND P RESENILIN : Regulated Intramembrane Proteolysis Links Development and Degeneration

Selkoe, D. J., & Kopan, R. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.041002.131334 · Cited by 640

Engineering synthetic vaccines using cues from natural immunity

Irvine, D. J., Swartz, M. A., & Szeto, G. L. (2013) · Nature Materials · doi:10.1038/nmat3775 · Cited by 605

A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells

Wang, X., Chang, W.-C., Wong, C. W., Colcher, D. M., Sherman, M. A., Ostberg, J. R., Forman, S. J., Riddell, S. R., & Jensen, M. C. (2011) · Blood · doi:10.1182/blood-2011-02-337360 · Cited by 605

Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs

Ferlazzo, G., Pack, M., Thomas, D. A., Paludan, C., Schmid, D., Strowig, T., Bougras-Cartron, G., Müller, W. A., Moretta, L., & Münz, C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407522101 · Cited by 583

T–cell mediated rejection of gene–modified HIV–specific cytotoxic T lymphocytes in HIV–infected patients

Riddell, S. R., Elliott, M., Lewinsohn, D. A., Gilbert, M. J., Wilson, L., Manley, S. A., Lupton, S. D., Overell, R. W., Reynolds, T. C., Corey, L., et al. (1996) · Nature Medicine · doi:10.1038/nm0296-216 · Cited by 564

Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’

Levin, A. M., Bates, D. L., Ring, A. M., Krieg, C., Lin, J. T., Su, L., Moraga, I., Raeber, M. E., Bowman, G. R., Novick, P. A., et al. (2012) · Nature · doi:10.1038/nature10975 · Cited by 562

Chimeric Receptors Providing Both Primary and Costimulatory Signaling in T Cells from a Single Gene Product

Finney, H. M., Lawson, A. D. G., Bebbington, C. R., & Weir, A. N. C. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.6.2791 · Cited by 545

Expression of a Functional CCR2 Receptor Enhances Tumor Localization and Tumor Eradication by Retargeted Human T cells Expressing a Mesothelin-Specific Chimeric Antibody Receptor

Moon, E. K., Carpenito, C., Sun, J., Wang, L. S., Kapoor, V., Predina, J. D., Powell, D. J., Riley, J. L., June, C. H., & Albelda, S. Μ. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0351 · Cited by 545

T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model

Di Stasi, A., De Angelis, B., Rooney, C. M., Zhang, L., Mahendravada, A., Foster, A. E., Heslop, H. E., Brenner, M. K., Dotti, G., & Savoldo, B. (2009) · Blood · doi:10.1182/blood-2009-03-209650 · Cited by 533

Enhanced Tumor Trafficking of GD2 Chimeric Antigen Receptor T Cells by Expression of the Chemokine Receptor CCR2b

Craddock, J. A., Lu, A., Bear, A. S., Pulè, M. A., Brenner, M. K., Rooney, C. M., & Foster, A. E. (2010) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181ee6675 · Cited by 514

Immune Regulation of Metabolic Homeostasis in Health and Disease

Brestoff, J. R., & Artis, D. (2015) · Cell · doi:10.1016/j.cell.2015.02.022 · Cited by 510

Dual Targeting of ErbB2 and MUC1 in Breast Cancer Using Chimeric Antigen Receptors Engineered to Provide Complementary Signaling

Wilkie, S., van Schalkwyk, M. C., Hobbs, S., Davies, D. M., van der Stegen, S. J. C., Pereira, A. C. P., Burbridge, S. E., Box, C., Eccles, S. A., & Maher, J. F. (2012) · Journal of Clinical Immunology · doi:10.1007/s10875-012-9689-9 · Cited by 491

Durability of Complete Responses in Patients With Metastatic Cancer Treated With High-Dose Interleukin-2

Rosenberg, S. A., Yang, J. C., White, D. E., & Steinberg, S. M. (1998) · Annals of Surgery · doi:10.1097/00000658-199809000-00004 · Cited by 486

Adoptive Transfer of Autologous Natural Killer Cells Leads to High Levels of Circulating Natural Killer Cells but Does Not Mediate Tumor Regression

Parkhurst, M. R., Riley, J. P., Dudley, M. E., & Rosenberg, S. A. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1347 · Cited by 477

T-Cell and NK-Cell Infiltration into Solid Tumors: A Key Limiting Factor for Efficacious Cancer Immunotherapy

Melero, I., Rouzaut, A., Motz, G. T., & Coukos, G. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0985 · Cited by 452

Cell-Based Therapeutics: The Next Pillar of Medicine

Fischbach, M. A., Bluestone, J. A., & Lim, W. A. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005568 · Cited by 424

How viruses hijack cell regulation

Davey, N. E., Travé, G., & Gibson, T. J. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.10.002 · Cited by 395

Structural basis for autoinhibition of Notch

Gordon, W. R., Vardar‐Ulu, D., Histen, G., Sanchez-Irizarry, C., Aster, J. C., & Blacklow, S. C. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1227 · Cited by 389

Mechanical Allostery: Evidence for a Force Requirement in the Proteolytic Activation of Notch

Gordon, W. R., Zimmerman, B., He, L., Miles, L., Huang, J., Tiyanont, K., McArthur, D. G., Aster, J. C., Perrimon, N., Loparo, J. J., et al. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.05.004 · Cited by 374

Prospects for gene-engineered T cell immunotherapy for solid cancers

Klebanoff, C. A., Rosenberg, S. A., & Restifo, N. P. (2016) · Nature Medicine · doi:10.1038/nm.4015 · Cited by 372

Chimeric Antigen Receptor Therapy for Cancer

Barrett, D. M., Singh, N., Porter, D. L., Grupp, S. A., & June, C. H. (2013) · Annual Review of Medicine · doi:10.1146/annurev-med-060512-150254 · Cited by 353

Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines.

Margolin, K. A., Rayner, A. A., Hawkins, M., Atkins, M. B., Dutcher, J. P., Fisher, R. I., Weiss, G. R., Doroshow, J. H., Jaffe, H. S., & Röper, M. (1989) · Journal of Clinical Oncology · doi:10.1200/jco.1989.7.4.486 · Cited by 346

Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo

Lanitis, E., Poussin, M., Klattenhoff, A. W., Song, D.-G., Sandaltzopoulos, R., June, C. H., & Powell, D. J. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0008 · Cited by 339

Insights into Cytokine–Receptor Interactions from Cytokine Engineering

Spangler, J. B., Moraga, I., Mendoza, J. L., & Garcia, K. C. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120211 · Cited by 304

Improving Adoptive T Cell Therapy by Targeting and Controlling IL-12 Expression to the Tumor Environment

Zhang, L., Kerkar, S. P., Yu, Z., Zheng, Z., Yang, S., Restifo, N. P., Rosenberg, S. A., & Morgan, R. A. (2011) · Molecular Therapy · doi:10.1038/mt.2010.313 · Cited by 301

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

Sykes, E. A., Dai, Q., Sarsons, C. D., Chen, J., Rocheleau, J. V., Hwang, D. M., Zheng, G., Cramb, D. T., Rinker, K. D., & Chan, W. C. W. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521265113 · Cited by 287

Immunoengineering: How Nanotechnology Can Enhance Cancer Immunotherapy

Goldberg, M. S. (2015) · Cell · doi:10.1016/j.cell.2015.03.037 · Cited by 281

Engineering GPCR signaling pathways with RASSLs

Conklin, B. R., Hsiao, E. C., Claeysen, S., Dumuis, A., Srinivasan, S., Forsayeth, J., Guettier, J., Chang, W. C., Pei, Y., McCarthy, K. D., et al. (2008) · Nature Methods · doi:10.1038/nmeth.1232 · Cited by 262

Tumor-Specific CD8+ T Cells Expressing Interleukin-12 Eradicate Established Cancers in Lymphodepleted Hosts

Kerkar, S. P., Muranski, P. J., Kaiser, A., Boni, A., Sanchez-Perez, L. A., Yu, Z., Palmer, D. C., Reger, R. N., Borman, Z. A., Zhang, L., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0735 · Cited by 254

Natural killer cell memory

Paust, S., & von Andrian, U. H. (2011) · Nature Immunology · doi:10.1038/ni.2032 · Cited by 238

Managing toxicities of high-dose interleukin-2.

Schwartz, R. N., Stover, L. L., & Dutcher, J. P. (2002) · PubMed · Cited by 235

Rapamycin Analogs with Differential Binding Specificity Permit Orthogonal Control of Protein Activity

Bayle, J. H., Grimley, J. S., Stankunas, K., Gestwicki, J. E., Wandless, T. J., & Crabtree, G. R. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2005.10.017 · Cited by 211

Levels of peripheral CD4+FoxP3+ regulatory T cells are negatively associated with clinical response to adoptive immunotherapy of human cancer

Yao, X., Ahmadzadeh, M., Lu, Y., Liewehr, D. J., Dudley, M. E., Liu, F., Schrump, D. S., Steinberg, S. M., Rosenberg, S. A., & Robbins, P. F. (2012) · Blood · doi:10.1182/blood-2011-10-386482 · Cited by 207

2B4 (CD244) Signaling by Recombinant Antigen-specific Chimeric Receptors Costimulates Natural Killer Cell Activation to Leukemia and Neuroblastoma Cells

Altvater, B., Landmeier, S., Pscherer, S., Temme, J., Schweer, K., Kailayangiri, S., Campana, D., Juergens, H., Pulè, M. A., & Rössig, C. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2810 · Cited by 207

Cutting Edge: Murine Dendritic Cells Require IL-15Rα to Prime NK Cells

Koka, R. M., Burkett, P. R., Chien, M., Chai, S., Boone, D. L., & Ma, A. I. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3594 · Cited by 201

Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas

Kruschinski, A., Moosmann, A., Poschke, I. C., Norell, H., Chmielewski, M. M., Seliger, B., Kiessling, R. W., Blankenstein, T. J. F., Abken, H., & Charo, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804788105 · Cited by 200

Targeting CD20+ Aggressive B-cell Non–Hodgkin Lymphoma by Anti-CD20 CAR mRNA-Modified Expanded Natural Killer Cells In Vitro and in NSG Mice

Chu, Y., Hochberg, J. C., Yahr, A., Ayello, J. S., van de Ven, C., Barth, M. J., Czuczman, M. S., & Cairo, M. S. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0114 · Cited by 177

A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies

Shimasaki, N., Fujisaki, H., Cho, D., Masselli, M., Lockey, T. D., Eldridge, P. W., Leung, W. H., & Campana, D. (2012) · Cytotherapy · doi:10.3109/14653249.2012.671519 · Cited by 176

Interleukin-2 Activity Can Be Fine Tuned with Engineered Receptor Signaling Clamps

Mitra, S., Ring, A. M., Amarnath, S., Spangler, J. B., Li, P., Ju, W., Fischer, S., Oh, J., Spolski, R. J., Weiskopf, K., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.04.018 · Cited by 175

A Tet-On Inducible System for Controlling CD19-Chimeric Antigen Receptor Expression upon Drug Administration

Sakemura, R. L., Terakura, S., Watanabe, K., Julamanee, J., Takagi, E., Miyao, K., Koyama, D., Goto, T., Hanajiri, R., Nishida, T., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0043 · Cited by 172

The Utility of Paradoxical Components in Biological Circuits

Hart, Y., & Alon, U. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.004 · Cited by 151

Therapeutic Potential of T Cell Chimeric Antigen Receptors (CARs) in Cancer Treatment: Counteracting Off-Tumor Toxicities for Safe CAR T Cell Therapy

Gross, G., & Eshhar, Z. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124844 · Cited by 149

FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions

Ahmadzadeh, M., Felipe-Silva, A., Heemskerk, B., Powell, D. J., Wunderlich, J. R., Merino, M. J., & Rosenberg, S. A. (2008) · Blood · doi:10.1182/blood-2008-06-163048 · Cited by 143

Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method

Li, L., Liu, L. N., Feller, S., Allen, C., Shivakumar, R., Fratantoni, J. C., Wolfraim, L. A., Fujisaki, H., Campana, D., Chopas, N., et al. (2009) · Cancer Gene Therapy · doi:10.1038/cgt.2009.61 · Cited by 143

The expanding universe of transposon technologies for gene and cell engineering

Ivics, Z., & Izsvák, Z. (2010) · Mobile DNA · doi:10.1186/1759-8753-1-25 · Cited by 134

The microanatomy of T‐cell responses

Lämmermann, T., & Sixt, M. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00592.x · Cited by 126

Increased Circulating Nitrogen Oxides After Human Tumor Immunotherapy: Correlation With Toxic Hemodynamic Changes

Ochoa, J. B., Curti, B. D., Peitzman, A. B., Simmons, R. L., Billiar, T. R., Hoffman, R. P., Rault, R., Longo, D., Urba, W. J., & Ochoa, A. C. (1992) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/84.11.864 · Cited by 125

Improving the safety of cell therapy with the TK-suicide gene

Greco, R., Oliveira, G., Stanghellini, M. T. L., Vago, L., Bondanza, A., Peccatori, J., Cieri, N., Marktel, S., Mastaglio, S., Bordignon, C., et al. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00095 · Cited by 122

Identification of New Melanoma Epitopes on Melanosomal Proteins Recognized by Tumor Infiltrating T Lymphocytes Restricted by HLA-A1, -A2, and -A3 Alleles

Kawakami, Y., Robbins, P. F., Wang, X., Tupesis, J. P., Parkhurst, M. R., Kang, X., Sakaguchi, K., Appella, E., & Rosenberg, S. A. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.12.6985 · Cited by 115

Optimization of the PiggyBac Transposon System for the Sustained Genetic Modification of Human T Lymphocytes

Nakazawa, Y., Huye, L. E., Dotti, G., Foster, A. E., Vera, J. F., Manuri, P. R., June, C. H., Rooney, C. M., & Wilson, M. H. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181ad762b · Cited by 113

Paradoxical Signaling by a Secreted Molecule Leads to Homeostasis of Cell Levels

Hart, Y., Reich-Zeliger, S., Antebi, Y. E., Zaretsky, I., Mayo, A., Alon, U. S., & Friedman, N. (2014) · Cell · doi:10.1016/j.cell.2014.07.033 · Cited by 105

Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal

Park, J. S., Rhau, B., Hermann, A., McNally, K. A., Zhou, C., Gong, D., Weiner, O. D., Conklin, B. R., Onuffer, J., & Lim, W. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402087111 · Cited by 102

Challenges and opportunities of allogeneic donor-derived CAR T cells

Yang, Y., Jacoby, E., & Fry, T. J. (2015) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000181 · Cited by 101

Design of chimeric antigen receptors with integrated controllable transient functions

Juillerat, A., Maréchal, A., Filhol, J.-M., Valton, J., Duclert, A., Poirot, L., & Duchateau, P. N. (2016) · Scientific Reports · doi:10.1038/srep18950 · Cited by 89

Myeloid Cells Obtained from the Blood but Not from the Tumor Can Suppress T-cell Proliferation in Patients with Melanoma

Gros, A., Turcotte, S., Wunderlich, J. R., Ahmadzadeh, M., Dudley, M. E., & Rosenberg, S. A. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1108 · Cited by 86

TCR-Engineered T Cells Meet New Challenges to Treat Solid Tumors: Choice of Antigen, T Cell Fitness, and Sensitization of Tumor Milieu

Kunert, A., Straetemans, T., Govers, C., Lamers, C., Mathijssen, R. H. J., Sleijfer, S., & Debets, R. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00363 · Cited by 77

Tumor cells escape suicide gene therapy by genetic and epigenetic instability

Frank, O. (2004) · Blood · doi:10.1182/blood-2004-03-0852 · Cited by 58

A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy

Narayanan, P., Lapteva, N., Seethammagari, M. R., Levitt, J. M., Slawin, K. M., & Spencer, D. M. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44327 · Cited by 55

Synthetic immunology: modulating the human immune system

Geering, B., & Fussenegger, M. (2014) · Trends in biotechnology · doi:10.1016/j.tibtech.2014.10.006 · Cited by 47

Evaluation of γ-Retroviral Vectors That Mediate the Inducible Expression of IL-12 for Clinical Application

Zhang, L., Feldman, S. A., Zheng, Z., Chinnasamy, N., Xu, H., Nahvi, A. V., Dudley, M. E., Rosenberg, S. A., & Morgan, R. A. (2012) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31825898e8 · Cited by 32

Grand Challenge Commentary: Synthetic immunology to engineer human immunity

Spiegel, D. A. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.477 · Cited by 27

Engineering cytokine receptors to control cellular functions

Kawahara, M., Ueda, H., & Nagamune, T. (2009) · Biochemical Engineering Journal · doi:10.1016/j.bej.2009.09.010 · Cited by 24

Selective expansion of genetically modified T cells using an antibody/interleukin-2 receptor chimera

Sogo, T., Kawahara, M., Tsumoto, K., Kumagai, I., Ueda, H., & Nagamune, T. (2008) · Journal of Immunological Methods · doi:10.1016/j.jim.2008.05.003 · Cited by 16

Tumour-intrinsic resistance to immune checkpoint blockade

Kalbasi, A. K., & Ribas, A. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0218-4 · Cited by 1,525

Reprogramming human T cell function and specificity with non-viral genome targeting

Roth, T. L., Puig-Saus, C., Yu, R., Shifrut, E., Carnevale, J., Li, P. J., Hiatt, J., Saco, J., Krystofinski, P., Li, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0326-5 · Cited by 839

Engineering the next generation of cell-based therapeutics

Bashor, C. J., Hilton, I. B., Bandukwala, H. S., Smith, D. M., & Omid Veiseh, A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00476-6 · Cited by 472

Engineering living therapeutics with synthetic biology

Cubillos-Ruiz, A., Guo, T., Sokolovska, A., Miller, P., Collins, J. J., Lu, T. K., & Lora, J. M. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00285-3 · Cited by 387

T cell receptor‐based cancer immunotherapy: Emerging efficacy and pathways of resistance

Chandran, S. S., & Klebanoff, C. A. (2019) · Immunological Reviews · doi:10.1111/imr.12772 · Cited by 337

Synthetic Biology Approaches in Immunology

Mohammad, N. B., Lam, C. C. K., & Truong, K. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b01081 · Cited by 6

Systems-synthetic biology in understanding the complexities and simple devices in immunology

Soni, B., Nimsarkar, P., Mol, M., Saha, B., & Singh, S. (2018) · Cytokine · doi:10.1016/j.cyto.2018.03.029 · Cited by 4

Synthetic biology-engineered immunotherapies: Precision control of immune responses

Wang, Z., Fu, W., Ding, Y.-F., Gao, C.-C., Qin, H.-Y., & Zhao, J.-L. (2026) · Biotechnology Advances · doi:10.1016/j.biotechadv.2026.108871 · Cited by 3

Synthetic Immunology—Building Immunity from the Bottom‐Up with Synthetic Cells

Staufer, O. (2024) · Advanced NanoBiomed Research · doi:10.1002/anbr.202400037 · Cited by 8

A synthetic biology approach to engineering circuits in immune cells

Hoces, D., Blanco, J. M., & Hernández-López, R. A. (2023) · Immunological Reviews · doi:10.1111/imr.13244 · Cited by 19