. 2013 Nov; 4:363.
doi: 10.3389/fimmu.2013.00363.

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

Andre Kunert 1 Trudy Straetemans  Coen Govers  Cor Lamers  Ron Mathijssen  Stefan Sleijfer  Reno Debets  
  • PMID: 24265631
  •     191 References
  •     39 citations


Adoptive transfer of T cells gene-engineered with antigen-specific T cell receptors (TCRs) has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to target immunogenic epitopes that are related to oncogenesis and selectively expressed by tumor tissue, and implement strategies that result in optimal T cell fitness. In addition, in particular for the treatment of solid tumors, it is equally necessary to include strategies that counteract the immune-suppressive nature of the tumor micro-environment. Here, we will provide an overview of the current status of TCR gene therapy, and redefine the following three challenges of improvement: "choice of target antigen"; "fitness of T cells"; and "sensitization of tumor milieu." We will categorize and discuss potential strategies to address each of these challenges, and argue that advancement of clinical TCR gene therapy critically depends on developments toward each of the three challenges.

Keywords: T cell avidity; T cell co-stimulation; T cells; TCR affinity; TCR transgenes; antigens; inhibitory micro-milieu; solid tumors.

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J Clin Invest, 2010 Oct 28; 120(11). PMID: 20978347    Free PMC article.
Recognition of NY-ESO-1+ tumor cells by engineered lymphocytes is enhanced by improved vector design and epigenetic modulation of tumor antigen expression.
Jennifer A Wargo, Paul F Robbins, +9 authors, Richard A Morgan.
Cancer Immunol Immunother, 2008 Aug 05; 58(3). PMID: 18677478    Free PMC article.
Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases.
Arcadi Cipponi, Marjorie Mercier, +7 authors, Nicolas van Baren.
Cancer Res, 2012 Aug 02; 72(16). PMID: 22850419
Treating cancer with genetically engineered T cells.
Tristen S Park, Steven A Rosenberg, Richard A Morgan.
Trends Biotechnol, 2011 Jun 15; 29(11). PMID: 21663987    Free PMC article.
Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b.
John A Craddock, An Lu, +4 authors, Aaron E Foster.
J Immunother, 2010 Sep 16; 33(8). PMID: 20842059    Free PMC article.
Highly Cited.
CD8 alpha coreceptor to improve TCR gene transfer to treat melanoma: down-regulation of tumor-specific production of IL-4, IL-5, and IL-10.
Ralph A Willemsen, Zsolt Sebestyén, +3 authors, Reno Debets.
J Immunol, 2006 Jul 05; 177(2). PMID: 16818755
Tumor-specific Th17-polarized cells eradicate large established melanoma.
Pawel Muranski, Andrea Boni, +14 authors, Nicholas P Restifo.
Blood, 2008 Mar 21; 112(2). PMID: 18354038    Free PMC article.
Highly Cited.
A human memory T cell subset with stem cell-like properties.
Luca Gattinoni, Enrico Lugli, +14 authors, Nicholas P Restifo.
Nat Med, 2011 Sep 20; 17(10). PMID: 21926977    Free PMC article.
Highly Cited.
Posttranscriptional control of T cell effector function by aerobic glycolysis.
Chih-Hao Chang, Jonathan D Curtis, +11 authors, Erika L Pearce.
Cell, 2013 Jun 12; 153(6). PMID: 23746840    Free PMC article.
Highly Cited.
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.
James N Kochenderfer, Mark E Dudley, +15 authors, Steven A Rosenberg.
Blood, 2011 Dec 14; 119(12). PMID: 22160384    Free PMC article.
Highly Cited.
Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients.
Michal J Besser, Ronnie Shapira-Frommer, +17 authors, Jacob Schachter.
Clin Cancer Res, 2010 Apr 22; 16(9). PMID: 20406835
Highly Cited.
Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy.
Gavin M Bendle, Carsten Linnemann, +11 authors, Ton N M Schumacher.
Nat Med, 2010 Apr 20; 16(5). PMID: 20400962
Highly Cited.
Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy.
Ronald J Buckanovich, Andrea Facciabene, +7 authors, George Coukos.
Nat Med, 2007 Dec 25; 14(1). PMID: 18157142
Highly Cited.
Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia.
Oliver Goodyear, Angelo Agathanggelou, +8 authors, Charles Craddock.
Blood, 2010 Jun 10; 116(11). PMID: 20530795
Highly Cited.
Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance.
F M Marincola, E M Jaffee, D J Hicklin, S Ferrone.
Adv Immunol, 1999 Dec 22; 74. PMID: 10605607
Highly Cited. Review.
Assessing the safety of cytotoxic T lymphocytes transduced with a dominant negative transforming growth factor-beta receptor.
Kristine Lacuesta, Elizabeth Buza, +10 authors, Catherine M Bollard.
J Immunother, 2006 May 16; 29(3). PMID: 16699368
Inducible apoptosis as a safety switch for adoptive cell therapy.
Antonio Di Stasi, Siok-Keen Tey, +17 authors, Malcolm K Brenner.
N Engl J Med, 2011 Nov 04; 365(18). PMID: 22047558    Free PMC article.
Highly Cited.
Nivolumab plus ipilimumab in advanced melanoma.
Jedd D Wolchok, Harriet Kluger, +21 authors, Mario Sznol.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724867    Free PMC article.
Highly Cited.
Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase.
Andrea Schietinger, Mary Philip, +2 authors, Hans Schreiber.
J Exp Med, 2010 Oct 06; 207(11). PMID: 20921286    Free PMC article.
Generation of human tumor-reactive cytotoxic T cells against peptides presented by non-self HLA class I molecules.
E Sadovnikova, L A Jopling, K S Soo, H J Stauss.
Eur J Immunol, 1998 Mar 04; 28(1). PMID: 9485199
An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins.
J C Skipper, R C Hendrickson, +9 authors, V H Engelhard.
J Exp Med, 1996 Feb 01; 183(2). PMID: 8627164    Free PMC article.
Highly Cited.
Tumor microenvironment and lymphocyte infiltration.
Gwendoline Rahir, Muriel Moser.
Cancer Immunol Immunother, 2012 Apr 11; 61(6). PMID: 22488275
Incorporation of transmembrane hydrophobic mutations in the TCR enhance its surface expression and T cell functional avidity.
Astar Haga-Friedman, Miryam Horovitz-Fried, Cyrille J Cohen.
J Immunol, 2012 May 01; 188(11). PMID: 22544927
Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen.
Christophe Lurquin, Bernard Lethé, +5 authors, Thierry Boon.
J Exp Med, 2005 Jan 20; 201(2). PMID: 15657294    Free PMC article.
Relapse or eradication of cancer is predicted by peptide-major histocompatibility complex affinity.
Boris Engels, Victor H Engelhard, +7 authors, Hans Schreiber.
Cancer Cell, 2013 Apr 20; 23(4). PMID: 23597565    Free PMC article.
Blockade of myeloid-derived suppressor cells after induction of lymphopenia improves adoptive T cell therapy in a murine model of melanoma.
Krithika N Kodumudi, Amy Weber, Amod A Sarnaik, Shari Pilon-Thomas.
J Immunol, 2012 Oct 27; 189(11). PMID: 23100512    Free PMC article.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Antigen-processing machinery breakdown and tumor growth.
B Seliger, M J Maeurer, S Ferrone.
Immunol Today, 2000 Aug 23; 21(9). PMID: 10953098
T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells.
A A Lighvani, D M Frucht, +8 authors, J J O'Shea.
Proc Natl Acad Sci U S A, 2001 Dec 26; 98(26). PMID: 11752460    Free PMC article.
Highly Cited.
Epigenetic modulation to enable antigen-specific T-cell therapy of colorectal cancer.
Jeffrey Chou, Lilien N Voong, +6 authors, Edus H Warren.
J Immunother, 2012 Feb 07; 35(2). PMID: 22306901    Free PMC article.
Comparison between computational alanine scanning and per-residue binding free energy decomposition for protein-protein association using MM-GBSA: application to the TCR-p-MHC complex.
Vincent Zoete, Olivier Michielin.
Proteins, 2007 Mar 23; 67(4). PMID: 17377991
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok.
N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810
Highly Cited.
A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer.
Elisa Kieback, Jehad Charo, +2 authors, Wolfgang Uckert.
Proc Natl Acad Sci U S A, 2008 Jan 10; 105(2). PMID: 18182487    Free PMC article.
Tumor-specific CD4+ T cells have a major "post-licensing" role in CTL mediated anti-tumor immunity.
A L Marzo, B F Kinnear, +4 authors, B Scott.
J Immunol, 2000 Nov 22; 165(11). PMID: 11086036
Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma.
Paulo C Rodriguez, Claudia P Hernandez, +5 authors, Augusto C Ochoa.
J Exp Med, 2005 Sep 28; 202(7). PMID: 16186186    Free PMC article.
Highly Cited.
Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells.
Beatrice Schuler-Thurner, Erwin S Schultz, +8 authors, Gerold Schuler.
J Exp Med, 2002 May 22; 195(10). PMID: 12021308    Free PMC article.
T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production.
Niels Schaft, Birgit Lankiewicz, +10 authors, Reno Debets.
Int Immunol, 2006 Mar 02; 18(4). PMID: 16507598
Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cells for the treatment of patients with metastatic melanoma.
Andreas Mackensen, Norbert Meidenbauer, +3 authors, Reinhard Andreesen.
J Clin Oncol, 2006 Nov 01; 24(31). PMID: 17075125
Highly Cited.
Combination of IL-21 and IL-15 enhances tumour-specific cytotoxicity and cytokine production of TCR-transduced primary T cells.
Nadine Pouw, Elike Treffers-Westerlaken, +4 authors, Reno Debets.
Cancer Immunol Immunother, 2010 Jan 27; 59(6). PMID: 20101507
MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines.
Bing Yang, Sean M O'Herrin, +11 authors, B Jack Longley.
Cancer Res, 2007 Oct 19; 67(20). PMID: 17942928
Selected murine residues endow human TCR with enhanced tumor recognition.
Gil Bialer, Miryam Horovitz-Fried, +2 authors, Cyrille J Cohen.
J Immunol, 2010 Apr 30; 184(11). PMID: 20427762
Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lineage malignancies.
Harjeet Singh, Matthew J Figliola, +9 authors, Laurence J N Cooper.
Cancer Res, 2011 May 12; 71(10). PMID: 21558388    Free PMC article.
Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy.
Richard A Morgan, Nachimuthu Chinnasamy, +28 authors, Steven A Rosenberg.
J Immunother, 2013 Feb 05; 36(2). PMID: 23377668    Free PMC article.
Highly Cited.
Cancer regression in patients after transfer of genetically engineered lymphocytes.
Richard A Morgan, Mark E Dudley, +13 authors, Steven A Rosenberg.
Science, 2006 Sep 02; 314(5796). PMID: 16946036    Free PMC article.
Highly Cited.
IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression.
Markus Chmielewski, Caroline Kopecky, Andreas A Hombach, Hinrich Abken.
Cancer Res, 2011 Jul 12; 71(17). PMID: 21742772
Highly Cited.
Helper T cell diversity and plasticity.
Shingo Nakayamada, Hayato Takahashi, Yuka Kanno, John J O'Shea.
Curr Opin Immunol, 2012 Feb 22; 24(3). PMID: 22341735    Free PMC article.
Highly Cited. Review.
Major histocompatibility complex class I and unique antigen expression by murine tumors that escaped from CD8+ T-cell-dependent surveillance.
P L Ward, H K Koeppen, +2 authors, H Schreiber.
Cancer Res, 1990 Jul 01; 50(13). PMID: 2112981
Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma.
Gerald P Linette, Edward A Stadtmauer, +20 authors, Carl H June.
Blood, 2013 Jun 19; 122(6). PMID: 23770775    Free PMC article.
Highly Cited.
Advances in understanding cancer genomes through second-generation sequencing.
Matthew Meyerson, Stacey Gabriel, Gad Getz.
Nat Rev Genet, 2010 Sep 18; 11(10). PMID: 20847746
Highly Cited. Review.
Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens.
Mark E Dudley, James C Yang, +17 authors, Steven A Rosenberg.
J Clin Oncol, 2008 Sep 24; 26(32). PMID: 18809613    Free PMC article.
Highly Cited.
Engineering higher affinity T cell receptors using a T cell display system.
Adam S Chervin, David H Aggen, John M Raseman, David M Kranz.
J Immunol Methods, 2008 Oct 16; 339(2). PMID: 18854190    Free PMC article.
Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity.
Christian S Hinrichs, Zachary A Borman, +14 authors, Nicholas P Restifo.
Proc Natl Acad Sci U S A, 2009 Oct 07; 106(41). PMID: 19805141    Free PMC article.
Highly Cited.
Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells.
Stefani Spranger, Robbert M Spaapen, +4 authors, Thomas F Gajewski.
Sci Transl Med, 2013 Aug 30; 5(200). PMID: 23986400    Free PMC article.
Highly Cited.
Slow down and survive: Enigmatic immunoregulation by BTLA and HVEM.
Theresa L Murphy, Kenneth M Murphy.
Annu Rev Immunol, 2010 Mar 24; 28. PMID: 20307212
About human tumor antigens to be used in immunotherapy.
S Lucas, P G Coulie.
Semin Immunol, 2008 Apr 09; 20(5). PMID: 18395462
Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function.
Rong Zeng, Rosanne Spolski, +9 authors, Warren J Leonard.
J Exp Med, 2005 Jan 05; 201(1). PMID: 15630141    Free PMC article.
Highly Cited.
Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer.
Elena Provasi, Pietro Genovese, +18 authors, Chiara Bonini.
Nat Med, 2012 Apr 03; 18(5). PMID: 22466705    Free PMC article.
Highly Cited.
Single-chain VαVβ T-cell receptors function without mispairing with endogenous TCR chains.
D H Aggen, A S Chervin, +8 authors, D M Kranz.
Gene Ther, 2011 Jul 15; 19(4). PMID: 21753797    Free PMC article.
Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control.
Michelle Hong, Anne-Laure Puaux, +8 authors, Jean-Pierre Abastado.
Cancer Res, 2011 Sep 29; 71(22). PMID: 21948969
Highly Cited.
Spontaneous regression of metastases from melanoma: review of the literature.
Louise Vennegaard Kalialis, Krzysztof T Drzewiecki, Helle Klyver.
Melanoma Res, 2009 Jul 28; 19(5). PMID: 19633580
Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer.
T Stanislawski, R H Voss, +9 authors, M Theobald.
Nat Immunol, 2001 Sep 29; 2(10). PMID: 11577350
Ovarian cancer progression is controlled by phenotypic changes in dendritic cells.
Uciane K Scarlett, Melanie R Rutkowski, +9 authors, Jose R Conejo-Garcia.
J Exp Med, 2012 Feb 22; 209(3). PMID: 22351930    Free PMC article.
Highly Cited.
Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations.
Keith T Flaherty, Jeffery R Infante, +23 authors, Jeffrey Weber.
N Engl J Med, 2012 Oct 02; 367(18). PMID: 23020132    Free PMC article.
Highly Cited.
Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells.
Cor H J Lamers, Ralph Willemsen, +7 authors, Jan W Gratama.
Blood, 2010 Oct 05; 117(1). PMID: 20889925
Highly Cited.
Single and dual amino acid substitutions in TCR CDRs can enhance antigen-specific T cell functions.
Paul F Robbins, Yong F Li, +12 authors, Steven A Rosenberg.
J Immunol, 2008 Apr 22; 180(9). PMID: 18424733    Free PMC article.
Highly Cited.
TCRs with high affinity for foreign pMHC show self-reactivity.
Phillip D Holler, Lukasz K Chlewicki, David M Kranz.
Nat Immunol, 2002 Dec 07; 4(1). PMID: 12469116
Adoptive transfer of cytotoxic T lymphocytes targeting two different antigens limits antigen loss and tumor escape.
Karen M Kaluza, Timothy Kottke, +3 authors, Richard Vile.
Hum Gene Ther, 2012 Jun 28; 23(10). PMID: 22734672    Free PMC article.
The genomic landscapes of human breast and colorectal cancers.
Laura D Wood, D Williams Parsons, +39 authors, Bert Vogelstein.
Science, 2007 Oct 13; 318(5853). PMID: 17932254
Highly Cited.
5-aza-2'-deoxycytidine-induced expression of functional cancer testis antigens in human renal cell carcinoma: immunotherapeutic implications.
Sandra Coral, Luca Sigalotti, +7 authors, Michele Maio.
Clin Cancer Res, 2002 Aug 13; 8(8). PMID: 12171902
Recruitment of monocytes/macrophages in different tumor microenvironments.
Heon-Woo Lee, Hyun-Jung Choi, +2 authors, Young-Guen Kwon.
Biochim Biophys Acta, 2013 Jan 05; 1835(2). PMID: 23287570
Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.
Omid Hamid, Caroline Robert, +23 authors, Antoni Ribas.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724846    Free PMC article.
Highly Cited.
Cooperation of human tumor-reactive CD4+ and CD8+ T cells after redirection of their specificity by a high-affinity p53A2.1-specific TCR.
Jürgen Kuball, Frank W Schmitz, +8 authors, Matthias Theobald.
Immunity, 2005 Jan 25; 22(1). PMID: 15664164
Human TCR that incorporate CD3zeta induce highly preferred pairing between TCRalpha and beta chains following gene transfer.
Zsolt Sebestyén, Erik Schooten, +9 authors, Reno Debets.
J Immunol, 2008 May 21; 180(11). PMID: 18490778
CAR-T cells and solid tumors: tuning T cells to challenge an inveterate foe.
David E Gilham, Reno Debets, +2 authors, Hinrich Abken.
Trends Mol Med, 2012 May 23; 18(7). PMID: 22613370
Minimal amino acid exchange in human TCR constant regions fosters improved function of TCR gene-modified T cells.
Daniel Sommermeyer, Wolfgang Uckert.
J Immunol, 2010 May 21; 184(11). PMID: 20483785
Cancer/testis (CT) antigens: potential targets for immunotherapy.
Otavia L Caballero, Yao-Tseng Chen.
Cancer Sci, 2009 Sep 02; 100(11). PMID: 19719775
Highly Cited. Review.
T cell receptor gene therapy: strategies for optimizing transgenic TCR pairing.
Coen Govers, Zsolt Sebestyén, +2 authors, Reno Debets.
Trends Mol Med, 2010 Feb 04; 16(2). PMID: 20122868
CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells.
Paul A Antony, Ciriaco A Piccirillo, +9 authors, Nicholas P Restifo.
J Immunol, 2005 Feb 25; 174(5). PMID: 15728465    Free PMC article.
Highly Cited.
Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.
Julie R Brahmer, Charles G Drake, +17 authors, Suzanne L Topalian.
J Clin Oncol, 2010 Jun 03; 28(19). PMID: 20516446    Free PMC article.
Highly Cited.
Human solid tumors contain high endothelial venules: association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer.
Ludovic Martinet, Ignacio Garrido, +5 authors, Jean-Philippe Girard.
Cancer Res, 2011 Aug 19; 71(17). PMID: 21846823
Highly Cited.
Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase.
Catherine Uyttenhove, Luc Pilotte, +5 authors, Benoît J Van den Eynde.
Nat Med, 2003 Sep 23; 9(10). PMID: 14502282
Highly Cited.
Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen.
M J Maeurer, S M Gollin, +7 authors, M T Lotze.
J Clin Invest, 1996 Oct 01; 98(7). PMID: 8833913    Free PMC article.
Targeting the Wilms tumor antigen 1 by TCR gene transfer: TCR variants improve tetramer binding but not the function of gene modified human T cells.
Sharyn Thomas, Shao-An Xue, +7 authors, Hans J Stauss.
J Immunol, 2007 Oct 20; 179(9). PMID: 17947653
Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain.
Jürgen Kuball, Beate Hauptrock, +6 authors, Philip D Greenberg.
J Exp Med, 2009 Jan 28; 206(2). PMID: 19171765    Free PMC article.
T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells.
Maryam Afkarian, John R Sedy, +5 authors, Kenneth M Murphy.
Nat Immunol, 2002 May 15; 3(6). PMID: 12006974
Highly Cited.
Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression.
Michel DuPage, Ann F Cheung, +6 authors, Tyler Jacks.
Cancer Cell, 2011 Jan 22; 19(1). PMID: 21251614    Free PMC article.
Highly Cited.
Bench, bedside, toolbox: T-cells deliver on every level.
Bruno Laugel.
Front Immunol, 2014 Feb 20; 5. PMID: 24550915    Free PMC article.
Recurrence of melanoma following T cell treatment: continued antigen expression in a tumor that evades T cell recruitment.
Trudy Straetemans, Cor Berrevoets, +8 authors, Reno Debets.
Mol Ther, 2014 Nov 05; 23(2). PMID: 25363716    Free PMC article.
T cell receptor-engineered T cells to treat solid tumors: T cell processing toward optimal T cell fitness.
Cor H J Lamers, Sabine van Steenbergen-Langeveld, +5 authors, Reno Debets.
Hum Gene Ther Methods, 2014 Nov 26; 25(6). PMID: 25423330    Free PMC article.
To affinity and beyond: harnessing the T cell receptor for cancer immunotherapy.
Jessica E Thaxton, Zihai Li.
Hum Vaccin Immunother, 2014 Dec 09; 10(11). PMID: 25483644    Free PMC article.
T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells.
M P Tan, A B Gerry, +8 authors, A K Sewell.
Clin Exp Immunol, 2014 Dec 17; 180(2). PMID: 25496365    Free PMC article.
Orchestrating an immune response against cancer with engineered immune cells expressing αβTCRs, CARs, and innate immune receptors: an immunological and regulatory challenge.
Moniek A de Witte, Guido J J Kierkels, +2 authors, Jürgen Kuball.
Cancer Immunol Immunother, 2015 May 21; 64(7). PMID: 25990073    Free PMC article.
Genetically modified T cells in cancer therapy: opportunities and challenges.
Michaela Sharpe, Natalie Mount.
Dis Model Mech, 2015 Jun 03; 8(4). PMID: 26035842    Free PMC article.
Favorable alteration of tumor microenvironment by immunomodulatory cytokines for efficient T-cell therapy in solid tumors.
Siri Tähtinen, Saija Kaikkonen, +5 authors, Akseli Hemminki.
PLoS One, 2015 Jun 25; 10(6). PMID: 26107883    Free PMC article.
Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice.
Simone Thomas, Sebastian Klobuch, +7 authors, Niels A W Lemmermann.
PLoS Pathog, 2015 Jul 17; 11(7). PMID: 26181057    Free PMC article.
Blockade of Programmed Death 1 Augments the Ability of Human T Cells Engineered to Target NY-ESO-1 to Control Tumor Growth after Adoptive Transfer.
Edmund K Moon, Raghuveer Ranganathan, +7 authors, Steven M Albelda.
Clin Cancer Res, 2015 Sep 02; 22(2). PMID: 26324743    Free PMC article.
Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.
Michael Hebeisen, Mathilde Allard, +3 authors, Nathalie Rufer.
Front Immunol, 2015 Dec 05; 6. PMID: 26635796    Free PMC article.
2015 Guidance on cancer immunotherapy development in early-phase clinical studies.
Guidance Development Review Committee, Working Group for Clinical Studies of Cancer Immunotherapy, +4 authors, Biostatistics Subcommittee.
Cancer Sci, 2016 Jan 16; 106(12). PMID: 26767933    Free PMC article.
Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient.
Imran Siddiqui, Marco Erreni, +2 authors, Paola Allavena.
J Immunother Cancer, 2016 Apr 21; 4. PMID: 27096098    Free PMC article.
Cellular Immune Responses and Immune Escape Mechanisms in Breast Cancer: Determinants of Immunotherapy.
Christoph Domschke, Andreas Schneeweiss, +6 authors, Florian Schuetz.
Breast Care (Basel), 2016 May 31; 11(2). PMID: 27239171    Free PMC article.
Is immunotherapy here to stay in multiple myeloma?
Paula Rodríguez-Otero, Bruno Paiva, +2 authors, Jesús F San Miguel.
Haematologica, 2017 Jan 14; 102(3). PMID: 28082344    Free PMC article.
Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.
Kole T Roybal, Wendell A Lim.
Annu Rev Immunol, 2017 Apr 28; 35. PMID: 28446063    Free PMC article.
Cancer Immunotherapy Using CAR-T Cells: From the Research Bench to the Assembly Line.
Diogo Gomes-Silva, Carlos A Ramos.
Biotechnol J, 2017 Sep 30; 13(2). PMID: 28960810    Free PMC article.
Clinical trials of CAR-T cells in China.
Bingshan Liu, Yongping Song, Delong Liu.
J Hematol Oncol, 2017 Oct 24; 10(1). PMID: 29058636    Free PMC article.
Highly Cited.
IL-2 mediates NK cell proliferation but not hyperactivity.
Richa Sharma, Asmita Das.
Immunol Res, 2017 Dec 20; 66(1). PMID: 29256180
Intra-tumoral production of IL18, but not IL12, by TCR-engineered T cells is non-toxic and counteracts immune evasion of solid tumors.
A Kunert, M Chmielewski, +3 authors, R Debets.
Oncoimmunology, 2018 Jan 04; 7(1). PMID: 29296541    Free PMC article.
PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer.
Qiongshu Li, Muyun Liu, +11 authors, Weibin Liu.
Oncol Lett, 2018 Mar 21; 15(4). PMID: 29556312    Free PMC article.
Tumor-Resident Dendritic Cells and Macrophages Modulate the Accumulation of TCR-Engineered T Cells in Melanoma.
Alastair Hotblack, Angelika Holler, +3 authors, Clare L Bennett.
Mol Ther, 2018 Apr 10; 26(6). PMID: 29628306    Free PMC article.
Adoptive cell transfer: new perspective treatment in veterinary oncology.
Joanna Katarzyna Bujak, Rafał Pingwara, Michelle Hase Nelson, Kinga Majchrzak.
Acta Vet Scand, 2018 Oct 12; 60(1). PMID: 30305130    Free PMC article.
Targeting cancers through TCR-peptide/MHC interactions.
Qinghua He, Xianhan Jiang, Xinke Zhou, Jinsheng Weng.
J Hematol Oncol, 2019 Dec 20; 12(1). PMID: 31852498    Free PMC article.
Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy.
Sophia Stock, Michael Schmitt, Leopold Sellner.
Int J Mol Sci, 2019 Dec 15; 20(24). PMID: 31835562    Free PMC article.
Cellular immunotherapy in multiple myeloma.
Manh-Cuong Vo, Thangaraj Jaya Lakshmi, +7 authors, Je-Jung Lee.
Korean J Intern Med, 2019 Feb 14; 34(5). PMID: 30754964    Free PMC article.
Immune-Checkpoint Blockade Opposes CD8+ T-cell Suppression in Human and Murine Cancer.
Lukas W Pfannenstiel, C Marcela Diaz-Montero, +3 authors, Brian R Gastman.
Cancer Immunol Res, 2019 Feb 08; 7(3). PMID: 30728151    Free PMC article.
The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review.
Jianxiang Zhang, Lingyu Wang.
Technol Cancer Res Treat, 2019 Feb 26; 18. PMID: 30798772    Free PMC article.
Highly Cited. Systematic Review.
TCR-like antibodies in cancer immunotherapy.
Qinghua He, Zhaoyu Liu, +3 authors, Jinsheng Weng.
J Hematol Oncol, 2019 Sep 16; 12(1). PMID: 31521180    Free PMC article.
T Cells Expressing a TCR-Like Antibody Selected Against the Heteroclitic Variant of a Shared MAGE-A Epitope Do Not Recognise the Cognate Epitope.
Mesha Saeed, Erik Schooten, +3 authors, Reno Debets.
Cancers (Basel), 2020 May 21; 12(5). PMID: 32429338    Free PMC article.
Identification of α-fetoprotein-specific T-cell receptors for hepatocellular carcinoma immunotherapy.
Wei Zhu, Yibing Peng, +10 authors, Yukai He.
Hepatology, 2018 Feb 15; 68(2). PMID: 29443377    Free PMC article.
The Whole Body as the System in Systems Immunology.
Maya M L Poon, Donna L Farber.
iScience, 2020 Sep 14; 23(9). PMID: 32920485    Free PMC article.
Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy.
Anne M Macpherson, Simon C Barry, Carmela Ricciardelli, Martin K Oehler.
J Clin Med, 2020 Sep 18; 9(9). PMID: 32937961    Free PMC article.
Liposomes targeted to MHC-restricted antigen improve drug delivery and antimelanoma response.
Mesha Saeed, Sara Zalba, +2 authors, Timo L M Ten Hagen.
Int J Nanomedicine, 2019 Apr 17; 14. PMID: 30988609    Free PMC article.
Lack of B and T cell reactivity towards IDH1R132H in blood and tumor tissue from LGG patients.
Bas Weenink, Mandy van Brakel, +3 authors, Reno Debets.
J Neurooncol, 2019 Jun 27; 144(1). PMID: 31240524    Free PMC article.
Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system.
Xiaohui Wang, Zhiqiang Wu, +3 authors, Weidong Han.
Front Med, 2020 Aug 15; 14(6). PMID: 32794014
Leveraging TCR Affinity in Adoptive Immunotherapy against Shared Tumor/Self-Antigens.
Aaron M Miller, Milad Bahmanof, +2 authors, Stephen P Schoenberger.
Cancer Immunol Res, 2018 Nov 30; 7(1). PMID: 30482746    Free PMC article.
DES-Tcell is a knowledgebase for exploring immunology-related literature.
Ahdab AlSaieedi, Adil Salhi, +7 authors, Magbubah Essack.
Sci Rep, 2021 Jul 14; 11(1). PMID: 34253812    Free PMC article.
Combined overexpression of four transcription factors promotes effector T cell dedifferentiation toward early phenotypes.
Lijun Yan, Yusheng Ou, +8 authors, Fenglin Wu.
Immunogenetics, 2022 Jan 11; 74(2). PMID: 35001141