Current landscape and future directions of bispecific antibodies in cancer immunotherapy

The PD-L1/4-1BB bispecific Antibody-Anticalin fusion protein PRS-344/S095012 elicits strong T-cell stimulation in a tumor-localized manner

(2022) Janet K. Peper-Gabriel et al.   CLINICAL CANCER RESEARCH

A trispecific antibody targeting HER2 and T cells inhibits breast cancer growth via CD4 cells

(2022) Edward Seung et al.   NATURE

Immunostimulatory Cancer-Associated Fibroblast Subpopulations Can Predict Immunotherapy Response in Head and Neck Cancer

(2022) Aleksandar Obradovic et al.   CLINICAL CANCER RESEARCH

Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology

(2022) John A. Thompson et al.   Journal of the National Comprehensive Cancer Network

Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders

(2022) Nicholas A. Maskalenko et al.   NATURE REVIEWS DRUG DISCOVERY

Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors

(2022) Alexander Muik et al.   Cancer Discovery

Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors

(2021) Matthew D. Hellmann et al.   CLINICAL CANCER RESEARCH

Design and efficacy of a monovalent bispecific PD-1/CTLA-4 antibody that enhances CTLA-4 blockade on PD-1+ activated T cells

(2021) Simon J Dovedi et al.   Cancer Discovery

B7-H3×4-1BB bispecific antibody augments antitumor immunity by enhancing terminally differentiated CD8+ tumor-infiltrating lymphocytes

(2021) Gihoon You et al.   Science Advances

Combinatorial targeting of multiple myeloma by complementing T cell engaging antibody fragments

(2021) Maria Geis et al.   Communications Biology

Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma

(2021) Kevin Bi et al.   CANCER CELL

First time intravesically administered trifunctional antibody catumaxomab in patients with recurrent non-muscle invasive bladder cancer indicates high tolerability and local immunological activity

(2021) Peter Ruf et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells

(2021) Rui Yang et al.   Frontiers in Immunology

Mesothelin is a novel cell surface disease marker and potential therapeutic target in acute myeloid leukemia

(2021) Allison J. Kaeding et al.   Blood Advances

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma

(2021) Paul Nathan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Antitumor efficacy and reduced toxicity using an anti-CD137 Probody therapeutic

(2021) Iñaki Etxeberria et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Novel anti-4-1BB×PD-L1 bispecific antibody augments anti-tumor immunity through tumor-directed T-cell activation and checkpoint blockade

(2021) Seongju Jeong et al.   Journal for ImmunoTherapy of Cancer

Generation of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer

(2021) Tianhang Zhai et al.   Journal for ImmunoTherapy of Cancer

Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation

(2021) Jaikumar Duraiswamy et al.   CANCER CELL

A Novel Bispecific Antibody Targeting PD-L1 and VEGF With Combined Anti-Tumor Activities

(2021) Xiaopei Cui et al.   Frontiers in Immunology

Bispecific antibody-mediated redirection of NKG2D-CAR natural killer cells facilitates dual targeting and enhances antitumor activity

(2021) Congcong Zhang et al.   Journal for ImmunoTherapy of Cancer

Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells

(2021) Longchao Liu et al.   Nature Biomedical Engineering

NK cells for cancer immunotherapy

(2020) Noriko Shimasaki et al.   NATURE REVIEWS DRUG DISCOVERY

Immune checkpoint signaling and cancer immunotherapy

(2020) Xing He et al.   CELL RESEARCH

Challenges and strategies for next-generation bispecific antibody-based antitumor therapeutics

(2020) Heliang Li et al.   Cellular & Molecular Immunology

FS118, a Bispecific Antibody Targeting LAG-3 and PD-L1, Enhances T-Cell Activation Resulting in Potent Antitumor Activity

(2020) Matthew Kraman et al.   CLINICAL CANCER RESEARCH

T cell-engaging therapies — BiTEs and beyond

(2020) Maria-Elisabeth Goebeler et al.   Nature Reviews Clinical Oncology

Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer

(2020) Yann Kieffer et al.   Cancer Discovery

A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma

(2020) Nancy L. Bartlett et al.   BLOOD

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy

(2020) Janelle C. Waite et al.   Science Translational Medicine

Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody

(2020) Martina Geiger et al.   Nature Communications

Fibroblast activation protein-targeted-4-1BB ligand agonist amplifies effector functions of intratumoral T cells in human cancer

(2020) Marta Trüb et al.   Journal for ImmunoTherapy of Cancer

TGF-β suppresses type 2 immunity to cancer

(2020) Ming Liu et al.   NATURE

Cancer immunotherapy via targeted TGF-β signalling blockade in TH cells

(2020) Shun Li et al.   NATURE

Bispecific monoclonal antibodies for targeted immunotherapy of solid tumors: Recent advances and clinical trials

(2020) Seyed Samad Hosseini et al.   INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models

(2020) Dong-Hoon Yeom et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

CD24 targeting bi-specific antibody that simultaneously stimulates NKG2D enhances the efficacy of cancer immunotherapy

(2019) Yue Han et al.   JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

Taking a "BiTE out of ALL" - Blinautmomab approval for MRD positive ALL

(2019) Emily Curran et al.   BLOOD

Tumor-localized costimulatory T cell engagement by the 4-1BB/HER2 bispecific antibody-Anticalin fusion PRS-343

(2019) Marlon J Hinner et al.   CLINICAL CANCER RESEARCH

Diabody-Ig: a novel platform for the generation of multivalent and multispecific antibody molecules

(2019) Oliver Seifert et al.   mAbs

Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance

(2019) Micol Eleonora Fiori et al.   Molecular Cancer

A coiled-coil masking domain for selective activation of therapeutic antibodies

(2019) Vivian H. Trang et al.   NATURE BIOTECHNOLOGY

Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity

(2019) Laurent Gauthier et al.   CELL

Bispecific antibodies: a mechanistic review of the pipeline

(2019) Aran F. Labrijn et al.   NATURE REVIEWS DRUG DISCOVERY

Tumor-targeted 4-1BB agonists for combination with T cell bispecific antibodies as off-the-shelf therapy

(2019) Christina Claus et al.   Science Translational Medicine

Endometrial Tumor Microenvironment Alters Human NK Cell Recruitment, and Resident NK Cell Phenotype and Function

(2019) Clara Degos et al.   Frontiers in Immunology

Meflin-positive cancer-associated fibroblasts inhibit pancreatic carcinogenesis

(2019) Yasuyuki Mizutani et al.   CANCER RESEARCH

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

(2019) James Larkin et al.   NEW ENGLAND JOURNAL OF MEDICINE

CTX-8573, an Innate-Cell Engager Targeting BCMA, is a Highly Potent Multispecific Antibody for the Treatment of Multiple Myeloma

(2019) Jennifer Watkins-Yoon et al.   BLOOD

Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology

(2019) Karen A. Autio et al.   CLINICAL CANCER RESEARCH

Hypoxia-Activated PEGylated Conditional Aptamer/Antibody for Cancer Imaging with Improved Specificity

(2019) Fang Zhou et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

On-target restoration of a split T cell-engaging antibody for precision immunotherapy

(2019) Agnes Banaszek et al.   Nature Communications

Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia

(2018) Nicola Gökbuget et al.   BLOOD

A Rationally Designed Fully Human EGFRvIII:CD3-Targeted Bispecific Antibody Redirects Human T Cells to Treat Patient-derived Intracerebral Malignant Glioma

(2018) Patrick C. Gedeon et al.   CLINICAL CANCER RESEARCH

A first-in-human phase 1a study of the bispecific anti-DLL4/anti-VEGF antibody navicixizumab (OMP-305B83) in patients with previously treated solid tumors

(2018) Antonio Jimeno et al.   INVESTIGATIONAL NEW DRUGS

TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

(2018) Sanjeev Mariathasan et al.   NATURE

Bifunctional PD-1 × αCD3 × αCD33 fusion protein reverses adaptive immune escape in acute myeloid leukemia

(2018) Monika Herrmann et al.   BLOOD

Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity

(2018) Chien-Chun Steven Pai et al.   JOURNAL OF CLINICAL INVESTIGATION

Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3

(2018) Dionysos Slaga et al.   Science Translational Medicine

CD33/CD3-bispecific T-cell engaging (BiTE®) antibody construct targets monocytic AML myeloid-derived suppressor cells

(2018) Regina Jitschin et al.   Journal for ImmunoTherapy of Cancer

FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease

(2018) Emily Y. Jen et al.   CLINICAL CANCER RESEARCH

The Fc Domain of Immunoglobulin Is Sufficient to Bridge NK Cells with Virally Infected Cells

(2017) Hong-Sheng Dai et al.   IMMUNITY

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

(2017) Giovanni Martinelli et al.   JOURNAL OF CLINICAL ONCOLOGY

Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia

(2017) Hagop Kantarjian et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tethered-variable CL bispecific IgG: an antibody platform for rapid bispecific antibody screening

(2017) Hok Seon Kim et al.   PROTEIN ENGINEERING DESIGN & SELECTION

Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent

(2017) Alice O. Kamphorst et al.   SCIENCE

Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade

(2017) Martina Schmittnaegel et al.   Science Translational Medicine

Combined antiangiogenic and anti–PD-L1 therapy stimulates tumor immunity through HEV formation

(2017) Elizabeth Allen et al.   Science Translational Medicine

An anti–glypican 3/CD3 bispecific T cell–redirecting antibody for treatment of solid tumors

(2017) Takahiro Ishiguro et al.   Science Translational Medicine

ATTACK, a novel bispecific T cell-recruiting antibody with trivalent EGFR binding and monovalent CD3 binding for cancer immunotherapy

(2017) Seandean Lykke Harwood et al.   OncoImmunology

Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia

(2017) Donald A. Berry et al.   JAMA Oncology

Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma

(2016) A. Viardot et al.   BLOOD

Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking

(2016) Friederike Braig et al.   BLOOD

FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3–CCL2 Signaling

(2016) Xuguang Yang et al.   CANCER RESEARCH

A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

(2016) M. Bacac et al.   CLINICAL CANCER RESEARCH

Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study

(2016) Maria-Elisabeth Goebeler et al.   JOURNAL OF CLINICAL ONCOLOGY

RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis

(2016) P. Bru nker et al.   MOLECULAR CANCER THERAPEUTICS

The ever-expanding role of HIF in tumour and stromal biology

(2016) Edward L. LaGory et al.   NATURE CELL BIOLOGY

Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival

(2016) Jonas Kloepper et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeted Therapy and Checkpoint Immunotherapy Combinations for the Treatment of Cancer

(2016) Paul E. Hughes et al.   TRENDS IN IMMUNOLOGY

A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma

(2015) A. Rothe et al.   BLOOD

Bispecific antibodies

(2015) Roland E. Kontermann et al.   DRUG DISCOVERY TODAY

Endothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naive and bevacizumab-resistant glioblastoma

(2015) A. Scholz et al.   EMBO Molecular Medicine

Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism

(2015) C Krupka et al.   LEUKEMIA

A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19+tumor cells

(2015) Uwe Reusch et al.   mAbs

Therapeutic bispecific T-cell engager antibody targeting the intracellular oncoprotein WT1

(2015) Tao Dao et al.   NATURE BIOTECHNOLOGY

The future of immune checkpoint therapy

(2015) P. Sharma et al.   SCIENCE

T-cell ligands modulate the cytolytic activity of the CD33/CD3 BiTE antibody construct, AMG 330

(2015) G S Laszlo et al.   Blood Cancer Journal

Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia

(2014) K. Beldjord et al.   BLOOD

Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface

(2014) Steven M Lewis et al.   NATURE BIOTECHNOLOGY

Role of Angiopoietin-2 in Adaptive Tumor Resistance to VEGF Signaling Blockade

(2014) Nicolò Rigamonti et al.   Cell Reports

A Phase I, first-in-human, open label, dose escalation study of MGD007, a humanized gpA33 × CD3 dual-affinity re-targeting (DART®) protein in patients with relapsed/refractory metastatic colorectal carcinoma

(2014) Herbert Hurwitz et al.   Journal for ImmunoTherapy of Cancer

CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330

(2013) C. Krupka et al.   BLOOD

Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML

(2013) G. S. Laszlo et al.   BLOOD

Angiopoietin-2: An Attractive Target for Improved Antiangiogenic Tumor Therapy

(2013) D. Gerald et al.   CANCER RESEARCH

Ang-2-VEGF-A CrossMab, a Novel Bispecific Human IgG1 Antibody Blocking VEGF-A and Ang-2 Functions Simultaneously, Mediates Potent Antitumor, Antiangiogenic, and Antimetastatic Efficacy

(2013) Y. Kienast et al.   CLINICAL CANCER RESEARCH

Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies

(2013) Christoph Spiess et al.   NATURE BIOTECHNOLOGY

Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index

(2013) L. R. Desnoyers et al.   Science Translational Medicine

Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL

(2012) M. S. Topp et al.   BLOOD

Catumaxomab

(2012) James E. Frampton   DRUGS

Regression of Human Prostate Cancer Xenografts in Mice by AMG 212/BAY2010112, a Novel PSMA/CD3-Bispecific BiTE Antibody Cross-Reactive with Non-Human Primate Antigens

(2012) M. Friedrich et al.   MOLECULAR CANCER THERAPEUTICS

Monoclonal TCR-redirected tumor cell killing

(2012) Nathaniel Liddy et al.   NATURE MEDICINE

Application of dual affinity retargeting molecules to achieve optimal redirected T-cell killing of B-cell lymphoma

(2011) P. A. Moore et al.   BLOOD

Targeting the ANG2/TIE2 Axis Inhibits Tumor Growth and Metastasis by Impairing Angiogenesis and Disabling Rebounds of Proangiogenic Myeloid Cells

(2011) Roberta Mazzieri et al.   CANCER CELL

Basic and Therapeutic Aspects of Angiogenesis

(2011) Michael Potente et al.   CELL

Strategies for extended serum half-life of protein therapeutics

(2011) Roland E Kontermann   CURRENT OPINION IN BIOTECHNOLOGY

Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies

(2011) W. Schaefer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM×anti-CD3) as a targeted cancer immunotherapy

(2010) Diane Seimetz et al.   CANCER TREATMENT REVIEWS

The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial

(2010) Markus M. Heiss et al.   INTERNATIONAL JOURNAL OF CANCER

Effector Cell Recruitment with Novel Fv-based Dual-affinity Re-targeting Protein Leads to Potent Tumor Cytolysis and in Vivo B-cell Depletion

(2010) Syd Johnson et al.   JOURNAL OF MOLECULAR BIOLOGY

Structural and functional characterization of the trifunctional antibody catumaxomab

(2010) Dirk Chelius et al.   mAbs

Catumaxomab

(2010) Rolf Linke et al.   mAbs

Host-Derived Angiopoietin-2 Affects Early Stages of Tumor Development and Vessel Maturation but Is Dispensable for Later Stages of Tumor Growth

(2009) Patrick Nasarre et al.   CANCER RESEARCH

Control of vascular morphogenesis and homeostasis through the angiopoietin–Tie system

(2009) Hellmut G. Augustin et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY