. 2021 Jan; 13(2):.
doi: 10.3390/cancers13020287.

Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors

Jim Middelburg 1 Kristel Kemper 2 Patrick Engelberts 2 Aran F Labrijn 2 Janine Schuurman 2 Thorbald van Hall 1 
  • PMID: 33466732
  •     199 References
  •     10 citations


Immunotherapy of cancer with CD3-bispecific antibodies is an approved therapeutic option for some hematological malignancies and is under clinical investigation for solid cancers. However, the treatment of solid tumors faces more pronounced hurdles, such as increased on-target off-tumor toxicities, sparse T-cell infiltration and impaired T-cell quality due to the presence of an immunosuppressive tumor microenvironment, which affect the safety and limit efficacy of CD3-bispecific antibody therapy. In this review, we provide a brief status update of the CD3-bispecific antibody therapy field and identify intrinsic hurdles in solid cancers. Furthermore, we describe potential combinatorial approaches to overcome these challenges in order to generate selective and more effective responses.

Keywords: CD3-bispecific antibody; T-cell co-stimulation; T-cell engager; antibody therapy; immuno-oncology; on-target off-tumor toxicity; solid tumors; tumor-associated antigens.

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Biochem Biophys Res Commun, 2019 May 03; 514(2). PMID: 31043272
Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3.
Dionysos Slaga, Diego Ellerman, +15 authors, Teemu T Junttila.
Sci Transl Med, 2018 Oct 20; 10(463). PMID: 30333240
Enhanced ADCC and NK Cell Activation of an Anticarcinoma Bispecific Antibody by Genetic Insertion of a Modified IL-15 Cross-linker.
Joerg U Schmohl, Martin Felices, +2 authors, Daniel A Vallera.
Mol Ther, 2016 May 10; 24(7). PMID: 27157665    Free PMC article.
Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager.
Jana de Sostoa, Carlos Alberto Fajardo, +3 authors, Ramon Alemany.
J Immunother Cancer, 2019 Jan 27; 7(1). PMID: 30683154    Free PMC article.
Highly Cited.
A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy.
Alessandro Satta, Giulia Grazia, +8 authors, Mariangela Figini.
Front Immunol, 2019 Nov 12; 10. PMID: 31708930    Free PMC article.
Depletion of regulatory T cells in tumors with an anti-CD25 immunotoxin induces CD8 T cell-mediated systemic antitumor immunity.
Masanori Onda, Kazuto Kobayashi, Ira Pastan.
Proc Natl Acad Sci U S A, 2019 Feb 15; 116(10). PMID: 30760587    Free PMC article.
CARs versus BiTEs: A Comparison between T Cell-Redirection Strategies for Cancer Treatment.
Clare Y Slaney, Pin Wang, Phillip K Darcy, Michael H Kershaw.
Cancer Discov, 2018 Jul 18; 8(8). PMID: 30012854
Highly Cited. Review.
Collagen density regulates the activity of tumor-infiltrating T cells.
Dorota E Kuczek, Anne Mette H Larsen, +12 authors, Daniel H Madsen.
J Immunother Cancer, 2019 Mar 15; 7(1). PMID: 30867051    Free PMC article.
Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy.
David T Teachey, Susan R Rheingold, +11 authors, Stephan A Grupp.
Blood, 2013 May 17; 121(26). PMID: 23678006    Free PMC article.
Highly Cited.
Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1.
Junpeng Qi, Xiuling Li, +5 authors, Christoph Rader.
Proc Natl Acad Sci U S A, 2018 May 31; 115(24). PMID: 29844189    Free PMC article.
Hybrid pH-sensitive nanogels surface-functionalized with collagenase for enhanced tumor penetration.
Xin Wang, Jie Luo, +4 authors, Rupei Tang.
J Colloid Interface Sci, 2018 May 02; 525. PMID: 29709781
T cell engaging bispecific antibody (T-BsAb): From technology to therapeutics.
Z Wu, N V Cheung.
Pharmacol Ther, 2017 Aug 24; 182. PMID: 28834699    Free PMC article.
Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways.
Ping Wee, Zhixiang Wang.
Cancers (Basel), 2017 May 18; 9(5). PMID: 28513565    Free PMC article.
Highly Cited. Review.
A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors.
Marina Bacac, Tanja Fauti, +25 authors, Pablo Umaña.
Clin Cancer Res, 2016 Feb 11; 22(13). PMID: 26861458
Highly Cited.
Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice.
Hong Qin, Beatrisa Lerman, +11 authors, Larry W Kwak.
Nat Med, 2014 May 27; 20(6). PMID: 24859530    Free PMC article.
CD3 bispecific antibody-induced cytokine release is dispensable for cytotoxic T cell activity.
Ji Li, Robert Piskol, +9 authors, Teemu T Junttila.
Sci Transl Med, 2019 Sep 06; 11(508). PMID: 31484792
Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines.
Michael A Morse, Amy C Hobeika, +4 authors, Timothy M Clay.
Blood, 2008 Jun 04; 112(3). PMID: 18519811    Free PMC article.
Highly Cited.
Immunotherapy targeting fibroblast activation protein inhibits tumor growth and increases survival in a murine colon cancer model.
Yuan Wen, Chun-Ting Wang, +7 authors, Yu-Quan Wei.
Cancer Sci, 2010 Sep 02; 101(11). PMID: 20804499
Phase 1 Dose Escalation Study of MEDI-565, a Bispecific T-Cell Engager that Targets Human Carcinoembryonic Antigen, in Patients With Advanced Gastrointestinal Adenocarcinomas.
Michael Pishvaian, Michael A Morse, +7 authors, Crystal S Denlinger.
Clin Colorectal Cancer, 2016 Sep 07; 15(4). PMID: 27591895
TEIPP antigens for T-cell based immunotherapy of immune-edited HLA class Ilow cancers.
Koen A Marijt, Elien M Doorduijn, Thorbald van Hall.
Mol Immunol, 2018 Apr 09; 113. PMID: 29627136
Inhibiting myeloid-derived suppressor cell trafficking enhances T cell immunotherapy.
Lillian Sun, Paul E Clavijo, +12 authors, Clint T Allen.
JCI Insight, 2019 Apr 05; 4(7). PMID: 30944253    Free PMC article.
Highly Cited.
CD33/CD3-bispecific T-cell engaging (BiTE®) antibody construct targets monocytic AML myeloid-derived suppressor cells.
Regina Jitschin, Domenica Saul, +7 authors, Dimitrios Mougiakakos.
J Immunother Cancer, 2018 Nov 07; 6(1). PMID: 30396365    Free PMC article.
Selection for Anti-transferrin Receptor Bispecific T-cell Engager in Different Molecular Formats.
Ming-Peng Fu, Zi-Long Guo, +4 authors, Ping Lei.
Curr Med Sci, 2020 Mar 14; 40(1). PMID: 32166662
CEA/CD3-bispecific T cell-engaging (BiTE) antibody-mediated T lymphocyte cytotoxicity maximized by inhibition of both PD1 and PD-L1.
Takuya Osada, Sandip P Patel, +3 authors, H Kim Lyerly.
Cancer Immunol Immunother, 2015 Mar 07; 64(6). PMID: 25742933
5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity.
Julie Vincent, Grégoire Mignot, +7 authors, François Ghiringhelli.
Cancer Res, 2010 Apr 15; 70(8). PMID: 20388795
Highly Cited.
Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study.
Giovanni Martinelli, Nicolas Boissel, +10 authors, Anthony Stein.
J Clin Oncol, 2017 Mar 30; 35(16). PMID: 28355115
Highly Cited.
An Oncolytic Virus Expressing a T-cell Engager Simultaneously Targets Cancer and Immunosuppressive Stromal Cells.
Joshua D Freedman, Margaret R Duffy, +11 authors, Kerry D Fisher.
Cancer Res, 2018 Nov 20; 78(24). PMID: 30449733
Highly Cited.
Silencing Fc Domains in T cell-Engaging Bispecific Antibodies Improves T-cell Trafficking and Antitumor Potency.
Linlin Wang, Sayed Shahabuddin Hoseini, +2 authors, Nai-Kong Cheung.
Cancer Immunol Res, 2019 Oct 17; 7(12). PMID: 31615814    Free PMC article.
Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha.
Matthew Kraman, Paul J Bambrough, +6 authors, Douglas T Fearon.
Science, 2010 Nov 06; 330(6005). PMID: 21051638
Highly Cited.
Immune-checkpoint inhibitors for combating T-cell dysfunction in cancer.
Ewelina Grywalska, Marcin Pasiarski, Stanisław Góźdź, Jacek Roliński.
Onco Targets Ther, 2018 Oct 17; 11. PMID: 30323625    Free PMC article.
Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy.
Steven L Highfill, Yongzhi Cui, +5 authors, Crystal L Mackall.
Sci Transl Med, 2014 May 23; 6(237). PMID: 24848257    Free PMC article.
Highly Cited.
Development of PF-06671008, a Highly Potent Anti-P-cadherin/Anti-CD3 Bispecific DART Molecule with Extended Half-Life for the Treatment of Cancer.
Adam R Root, Wei Cao, +43 authors, Laird Bloom.
Antibodies (Basel), 2016 Mar 04; 5(1). PMID: 31557987    Free PMC article.
A comprehensive survey of Ras mutations in cancer.
Ian A Prior, Paul D Lewis, Carla Mattos.
Cancer Res, 2012 May 17; 72(10). PMID: 22589270    Free PMC article.
Highly Cited.
A review of bispecific antibodies and antibody constructs in oncology and clinical challenges.
Frans V Suurs, Marjolijn N Lub-de Hooge, Elisabeth G E de Vries, Derk Jan A de Groot.
Pharmacol Ther, 2019 Apr 28; 201. PMID: 31028837
Tregs activated by bispecific antibodies: Killers or suppressors?
Stefanie Koristka, Marc Cartellieri, +4 authors, Michael P Bachmann.
Oncoimmunology, 2015 May 08; 4(3). PMID: 25949920    Free PMC article.
A Novel Bispecific Antibody against Human CD3 and Ephrin Receptor A10 for Breast Cancer Therapy.
Shintaro Taki, Haruhiko Kamada, +6 authors, Shin-ichi Tsunoda.
PLoS One, 2015 Dec 19; 10(12). PMID: 26678395    Free PMC article.
Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab.
Kimberly M Lau, Ila M Saunders, Aaron M Goodman.
J Oncol Pharm Pract, 2020 Jul 02; 27(4). PMID: 32605497
Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade.
Rikke B Holmgaard, David A Schaer, +14 authors, Kyla E Driscoll.
J Immunother Cancer, 2018 Jun 06; 6(1). PMID: 29866156    Free PMC article.
Highly Cited.
Mechanisms regulating T-cell infiltration and activity in solid tumors.
E Lanitis, D Dangaj, M Irving, G Coukos.
Ann Oncol, 2017 Oct 19; 28(suppl_12). PMID: 29045511
Highly Cited.
The NKG2A-HLA-E Axis as a Novel Checkpoint in the Tumor Microenvironment.
Linda Borst, Sjoerd H van der Burg, Thorbald van Hall.
Clin Cancer Res, 2020 May 16; 26(21). PMID: 32409305
Relative lymphocyte count is a prognostic parameter in cancer patients with catumaxomab immunotherapy.
Michael Alfred Ströhlein, Rolf Lefering, Dirk Rolf Bulian, Markus Maria Heiss.
Med Hypotheses, 2014 Jan 15; 82(3). PMID: 24411128
Replication-selective oncolytic viruses in the treatment of cancer.
Bart Everts, Henk G van der Poel.
Cancer Gene Ther, 2004 Oct 09; 12(2). PMID: 15472714
A Mucin 16 bispecific T cell-engaging antibody for the treatment of ovarian cancer.
Alison Crawford, Lauric Haber, +27 authors, Jessica R Kirshner.
Sci Transl Med, 2019 Jun 21; 11(497). PMID: 31217340
The S1P-analog FTY720 differentially modulates T-cell homing via HEV: T-cell-expressed S1P1 amplifies integrin activation in peripheral lymph nodes but not in Peyer patches.
Cornelia Halin, M Lucila Scimone, +6 authors, Ulrich H von Andrian.
Blood, 2005 May 05; 106(4). PMID: 15870184    Free PMC article.
Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy.
Masaki Maruta, Toshiki Ochi, +6 authors, Masaki Yasukawa.
Sci Rep, 2019 Sep 19; 9(1). PMID: 31527633    Free PMC article.
Enhanced tumor-targeting selectivity by modulating bispecific antibody binding affinity and format valence.
Yariv Mazor, Kris F Sachsenmeier, +5 authors, William F Dall'Acqua.
Sci Rep, 2017 Jan 10; 7. PMID: 28067257    Free PMC article.
Proteases, extracellular matrix, and cancer: a workshop of the path B study section.
Yves A DeClerck, Arthur M Mercurio, +10 authors, Martin Padarathsingh.
Am J Pathol, 2004 Mar 25; 164(4). PMID: 15039201    Free PMC article.
TSNAdb: A Database for Tumor-specific Neoantigens from Immunogenomics Data Analysis.
Jingcheng Wu, Wenyi Zhao, +4 authors, Shuqing Chen.
Genomics Proteomics Bioinformatics, 2018 Sep 18; 16(4). PMID: 30223042    Free PMC article.
Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ.
Juan Dubrot, Francisca Milheiro, +11 authors, Ignacio Melero.
Cancer Immunol Immunother, 2010 Mar 26; 59(8). PMID: 20336294
Conventional and Chemically Programmed Asymmetric Bispecific Antibodies Targeting Folate Receptor 1.
Junpeng Qi, David Hymel, +2 authors, Christoph Rader.
Front Immunol, 2019 Sep 10; 10. PMID: 31497024    Free PMC article.
Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment.
Susanne M Steggerda, Mark K Bennett, +18 authors, Matthew I Gross.
J Immunother Cancer, 2017 Dec 20; 5(1). PMID: 29254508    Free PMC article.
Highly Cited.
A class of costimulatory CD28-bispecific antibodies that enhance the antitumor activity of CD3-bispecific antibodies.
Dimitris Skokos, Janelle C Waite, +44 authors, George D Yancopoulos.
Sci Transl Med, 2020 Jan 10; 12(525). PMID: 31915305
Differential binding of viral peptides to HLA-A2 alleles. Implications for human papillomavirus type 16 E7 peptide-based vaccination against cervical carcinoma.
M E Ressing, J H de Jong, +6 authors, C J Melief.
Eur J Immunol, 1999 May 06; 29(4). PMID: 10229097
Elements of cancer immunity and the cancer-immune set point.
Daniel S Chen, Ira Mellman.
Nature, 2017 Jan 20; 541(7637). PMID: 28102259
Highly Cited. Review.
Induction of human T lymphocyte cytotoxicity and inhibition of tumor growth by tumor-specific diabody-based molecules secreted from gene-modified bystander cells.
Belén Blanco, Phillip Holliger, Richard G Vile, Luis Alvarez-Vallina.
J Immunol, 2003 Jul 09; 171(2). PMID: 12847281
Targeting immunotherapy for bladder cancer using anti-CD3× B7-H3 bispecific antibody.
Wanru Ma, Juan Ma, +3 authors, Man Zhang.
Cancer Med, 2018 Sep 27; 7(10). PMID: 30253078    Free PMC article.
A library of Neo Open Reading Frame peptides (NOPs) as a sustainable resource of common neoantigens in up to 50% of cancer patients.
Jan Koster, Ronald H A Plasterk.
Sci Rep, 2019 May 01; 9(1). PMID: 31036835    Free PMC article.
The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial.
Markus M Heiss, Pawel Murawa, +17 authors, Simon L Parsons.
Int J Cancer, 2010 May 18; 127(9). PMID: 20473913    Free PMC article.
Highly Cited.
Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4.
Rikke B Holmgaard, Dmitriy Zamarin, +2 authors, James P Allison.
J Exp Med, 2013 Jun 12; 210(7). PMID: 23752227    Free PMC article.
Highly Cited.
Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3.
WanJun Chen, Wenwen Jin, +5 authors, Sharon M Wahl.
J Exp Med, 2003 Dec 17; 198(12). PMID: 14676299    Free PMC article.
Highly Cited.
Engineering Immune Cells for in vivo Secretion of Tumor-Specific T Cell-Redirecting Bispecific Antibodies.
Belén Blanco, Ángel Ramírez-Fernández, Luis Alvarez-Vallina.
Front Immunol, 2020 Sep 10; 11. PMID: 32903593    Free PMC article.
CAR T-cell Therapy: A New Era in Cancer Immunotherapy.
Androulla N Miliotou, Lefkothea C Papadopoulou.
Curr Pharm Biotechnol, 2018 Apr 19; 19(1). PMID: 29667553
Highly Cited. Review.
The bispecific anti-CD3 × anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer.
Huijun Zhao, Juan Ma, +2 authors, Man Zhang.
Invest New Drugs, 2018 Oct 31; 37(5). PMID: 30374653
Gene modification strategies for next-generation CAR T cells against solid cancers.
Yonggui Tian, Yilu Li, Yupei Shao, Yi Zhang.
J Hematol Oncol, 2020 May 20; 13(1). PMID: 32423475    Free PMC article.
Human T Cell Development, Localization, and Function throughout Life.
Brahma V Kumar, Thomas J Connors, Donna L Farber.
Immunity, 2018 Feb 22; 48(2). PMID: 29466753    Free PMC article.
Highly Cited. Review.
Checkpoint Antibodies but not T Cell-Recruiting Diabodies Effectively Synergize with TIL-Inducing γ-Irradiation.
Michael Hettich, Jayashree Lahoti, Shruthi Prasad, Gabriele Niedermann.
Cancer Res, 2016 Jun 16; 76(16). PMID: 27302161
Efficacy and Tolerability of a GD2-Directed Trifunctional Bispecific Antibody in a Preclinical Model: Subcutaneous Administration Is Superior to Intravenous Delivery.
Nina Deppisch, Peter Ruf, +4 authors, Ralph Mocikat.
Mol Cancer Ther, 2015 Jun 13; 14(8). PMID: 26063765
Targeting immunotherapy for bladder cancer by using anti-CD3 × CD155 bispecific antibody.
Wanru Ma, Juan Ma, +2 authors, Man Zhang.
J Cancer, 2019 Oct 12; 10(21). PMID: 31602268    Free PMC article.
Targeting CD133high Colorectal Cancer Cells In Vitro and In Vivo With an Asymmetric Bispecific Antibody.
Lei Zhao, Yudan Yang, +7 authors, Tao Zhang.
J Immunother, 2015 Jun 08; 38(6). PMID: 26049545
Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma.
Siler H Panowski, Tracy C Kuo, +27 authors, Barbra J Sasu.
Mol Cancer Ther, 2019 Aug 23; 18(11). PMID: 31434693
T-cell engager-armed oncolytic vaccinia virus significantly enhances antitumor therapy.
Feng Yu, Xingbing Wang, +3 authors, Xiao-Tong Song.
Mol Ther, 2013 Oct 19; 22(1). PMID: 24135899    Free PMC article.
Bispecific T-Cell Redirection versus Chimeric Antigen Receptor (CAR)-T Cells as Approaches to Kill Cancer Cells.
William R Strohl, Michael Naso.
Antibodies (Basel), 2019 Sep 24; 8(3). PMID: 31544847    Free PMC article.
Expression of inhibitory receptors on intratumoral T cells modulates the activity of a T cell-bispecific antibody targeting folate receptor.
Jens Schreiner, Daniela S Thommen, +16 authors, Alfred Zippelius.
Oncoimmunology, 2016 Apr 09; 5(2). PMID: 27057429    Free PMC article.
High throughput development of TCR-mimic antibody that targets survivin-2B80-88/HLA-A*A24 and its application in a bispecific T-cell engager.
Nobuyuki Kurosawa, Yuka Wakata, +2 authors, Masaharu Isobe.
Sci Rep, 2019 Jul 10; 9(1). PMID: 31285464    Free PMC article.
Daily ascending dosing in cynomolgus monkeys to mitigate cytokine release syndrome induced by ERY22, surrogate for T-cell redirecting bispecific antibody ERY974 for cancer immunotherapy.
Yoshika Iwata, Masanori Sasaki, +7 authors, Masayuki Mishima.
Toxicol Appl Pharmacol, 2019 Jul 22; 379. PMID: 31326447
Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy.
A Rotte, J Y Jin, V Lemaire.
Ann Oncol, 2017 Oct 27; 29(1). PMID: 29069302
Highly Cited. Review.
Immunotherapeutic Potential of TGF-β Inhibition and Oncolytic Viruses.
Christianne Groeneveldt, Thorbald van Hall, +2 authors, Nadine van Montfoort.
Trends Immunol, 2020 Apr 01; 41(5). PMID: 32223932
L-Arginine regulates the expression of the T-cell receptor zeta chain (CD3zeta) in Jurkat cells.
F Taheri, J B Ochoa, +5 authors, A C Ochoa.
Clin Cancer Res, 2001 Apr 13; 7(3 Suppl). PMID: 11300497
The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation.
Anne Månsson Kvarnhammar, Niina Veitonmäki, +16 authors, Peter Ellmark.
J Immunother Cancer, 2019 Apr 13; 7(1). PMID: 30975201    Free PMC article.
A Novel GUCY2C-CD3 T-Cell Engaging Bispecific Construct (PF-07062119) for the Treatment of Gastrointestinal Cancers.
Divya Mathur, Adam R Root, +24 authors, Puja Sapra.
Clin Cancer Res, 2020 Jan 31; 26(9). PMID: 31996389
CEA TCB: A novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors.
Marina Bacac, Christian Klein, Pablo Umana.
Oncoimmunology, 2016 Sep 14; 5(8). PMID: 27622073    Free PMC article.
Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment.
Stefani Spranger, Holly K Koblish, +3 authors, Thomas F Gajewski.
J Immunother Cancer, 2014 May 16; 2. PMID: 24829760    Free PMC article.
Highly Cited.
Efficient Generation of Bispecific Murine Antibodies for Pre-Clinical Investigations in Syngeneic Rodent Models.
Aran F Labrijn, Joyce I Meesters, +8 authors, Paul W H I Parren.
Sci Rep, 2017 Jun 01; 7(1). PMID: 28559564    Free PMC article.
EpCAM and its potential role in tumor-initiating cells.
Sannia Imrich, Matthias Hachmeister, Olivier Gires.
Cell Adh Migr, 2012 Jun 01; 6(1). PMID: 22647938    Free PMC article.
MEK Inhibitor Augments Antitumor Activity of B7-H3-Redirected Bispecific Antibody.
Hongjian Li, Cheng Huang, +11 authors, Aiping Tong.
Front Oncol, 2020 Sep 29; 10. PMID: 32984002    Free PMC article.
Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells.
Margherita Norelli, Barbara Camisa, +14 authors, Attilio Bondanza.
Nat Med, 2018 May 29; 24(6). PMID: 29808007
Highly Cited.
Bispecific antibodies: a mechanistic review of the pipeline.
Aran F Labrijn, Maarten L Janmaat, Janice M Reichert, Paul W H I Parren.
Nat Rev Drug Discov, 2019 Jun 09; 18(8). PMID: 31175342
Highly Cited. Review.
Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape.
Xianjie Jiang, Jie Wang, +12 authors, Zhaoyang Zeng.
Mol Cancer, 2019 Jan 17; 18(1). PMID: 30646912    Free PMC article.
Highly Cited. Review.
Manipulating IL-10 signalling blockade for better immunotherapy.
Guoying Ni, Tianfang Wang, +6 authors, Xiaosong Liu.
Cell Immunol, 2015 Jan 18; 293(2). PMID: 25596475
Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway.
Brian T Fife, Indira Guleria, +7 authors, Jeffrey A Bluestone.
J Exp Med, 2006 Nov 23; 203(12). PMID: 17116737    Free PMC article.
Highly Cited.
PD-1-mediated suppression of IL-2 production induces CD8+ T cell anergy in vivo.
Shunsuke Chikuma, Seigo Terawaki, +5 authors, Tasuku Honjo.
J Immunol, 2009 May 21; 182(11). PMID: 19454662
Design, selection and optimization of an anti-TRAIL-R2/anti-CD3 bispecific antibody able to educate T cells to recognize and destroy cancer cells.
Alessandro Satta, Delia Mezzanzanica, +9 authors, Mariangela Figini.
MAbs, 2018 Jul 12; 10(7). PMID: 29993310    Free PMC article.
Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics.
Xiaotian Zhong, Aaron M D'Antona.
Antibodies (Basel), 2021 Apr 04; 10(2). PMID: 33808165    Free PMC article.
A scDb-based trivalent bispecific antibody for T-cell-mediated killing of HER3-expressing cancer cells.
Nadine Aschmoneit, Sophia Steinlein, +2 authors, Roland E Kontermann.
Sci Rep, 2021 Jul 08; 11(1). PMID: 34230555    Free PMC article.
Co-Stimulatory Bispecific Antibodies Induce Enhanced T Cell Activation and Tumor Cell Killing in Breast Cancer Models.
Karsten M Warwas, Marten Meyer, +9 authors, Frank Momburg.
Front Immunol, 2021 Sep 07; 12. PMID: 34484225    Free PMC article.
The state of the art of bispecific antibodies for treating human malignancies.
Shuhang Wang, Kun Chen, +16 authors, Ning Li.
EMBO Mol Med, 2021 Aug 26; 13(9). PMID: 34431224    Free PMC article.
Nanoparticle T cell engagers for the treatment of acute myeloid leukemia.
Kinan Alhallak, Jennifer Sun, +9 authors, Abdel Kareem Azab.
Oncotarget, 2021 Sep 23; 12(19). PMID: 34548905    Free PMC article.
Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics.
Roland E Kontermann, Guy Ungerechts, Dirk M Nettelbeck.
MAbs, 2021 Nov 09; 13(1). PMID: 34747345    Free PMC article.
Fc-comprising scDb-based trivalent, bispecific T-cell engagers for selective killing of HER3-expressing cancer cells independent of cytokine release.
Nadine Aschmoneit, Lennart Kühl, Oliver Seifert, Roland E Kontermann.
J Immunother Cancer, 2021 Nov 17; 9(11). PMID: 34782429    Free PMC article.
Carboranes as unique pharmacophores in antitumor medicinal chemistry.
Yu Chen, Fukuan Du, +8 authors, Zhangang Xiao.
Mol Ther Oncolytics, 2022 Feb 11; 24. PMID: 35141397    Free PMC article.
A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity.
Yan Feng, Kun Xie, +8 authors, Jianmin Fang.
Life (Basel), 2022 Feb 26; 12(2). PMID: 35207448    Free PMC article.
Cancer cell-intrinsic resistance to BiTE therapy is mediated by loss of CD58 costimulation and modulation of the extrinsic apoptotic pathway.
Ye Shen, Jason S Eng, +5 authors, Olivier Nolan-Stevaux.
J Immunother Cancer, 2022 Mar 18; 10(3). PMID: 35296559    Free PMC article.