The promise of bispecific antibodies: Clinical applications and challenges

Lim, Sun Min; Pyo, Kyoung‐Ho; Soo, Ross A.; Cho, Byoung Chul

doi:10.1016/j.ctrv.2021.102240

Cited by 36 publications

(34 citation statements)

References 140 publications

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“…There are bispecific antibodies, such as BiTEs, that are synthetic antibody structures that bind to two separate epitopes, with intentions such as bridging tumor-immune cell interactions or increasing antibody specificity. An in-depth review of bispecific antibodies, including BiTEs, was recently presented by Lim et al [ 117 ]. Moreover, investigators recently developed multi-antigen prime-and-kill synNotch-CAR T cells that use a dual receptor circuit, the first of which detects EGFRvIII or a brain-specific myelin oligodendrocyte glycoprotein to induce expression of CARs against EphA2 and IL13Rα2 [ 118 ].…”

Section: Chimeric Antigen Receptor (Car) T Cellsmentioning

confidence: 99%

Advances in Immunotherapy for Adult Glioblastoma

Chokshi

Brakel

Tatari

et al. 2021

Cancers

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Despite aggressive multimodal therapy, glioblastoma (GBM) remains the most common malignant primary brain tumor in adults. With the advent of therapies that revitalize the anti-tumor immune response, several immunotherapeutic modalities have been developed for treatment of GBM. In this review, we summarize recent clinical and preclinical efforts to evaluate vaccination strategies, immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells. Although these modalities have shown long-term tumor regression in subsets of treated patients, the underlying biology that may predict efficacy and inform therapy development is being actively investigated. Common to all therapeutic modalities are fundamental mechanisms of therapy evasion by tumor cells, including immense intratumoral heterogeneity, suppression of the tumor immune microenvironment and low mutational burden. These insights have led efforts to design rational combinatorial therapies that can reignite the anti-tumor immune response, effectively and specifically target tumor cells and reliably decrease tumor burden for GBM patients.

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Section: Chimeric Antigen Receptor (Car) T Cellsmentioning

confidence: 99%

Advances in Immunotherapy for Adult Glioblastoma

Chokshi

Brakel

Tatari

et al. 2021

Cancers

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“…Since then, numerous novel technologies have emerged, dictating diverse pharmacokinetic and pharmacodynamic profiles [15]. In parallel, the discovery of novel targets, either on transformed or healthy (i.e., immune/stromal cells) tissues, as well as novel payloads (i.e., cytokines or chemotherapeutics), have supported the increasing use and testing of bsAbs in the last decades [16].…”

Section: Bispecific Antibodies Design and Developmentmentioning

confidence: 99%

“…Regardless of structure and design, bsAbs mechanisms of action can be summarized in immune cell engagement (ICEs), tumor associated antigen (TAA)-targeting, immune checkpoint blockade (ICBs), or Ab-drug conjugation (bsADCs) (Figure 1) [16].…”

Section: Mechanistic Classification Of Bispecific Antibodiesmentioning

confidence: 99%

“…Although many bsAbs showed remarkable activity especially in the context of B-ALL [24], most clinical trials so far have been conducted in patients with solid malignancies, as recapitulated in Tables S1 and S2 [16]. In this setting, most trials investigated Fc-bearing bsAbs (69%) either alone (approximately 50%) or in combination with immunotherapies or other agents (i.e., target therapies or chemotherapies) (Figure 2A,B).…”

Section: State-of-the Art Of Bispecific Antibodies In Solid Tumorsmentioning

confidence: 99%

“…recapitulated in Tables S1 and S2 [16]. In this setting, most trials investigated Fc-bearing bsAbs (69%) either alone (approximately 50%) or in combination with immunotherapies or other agents (i.e., target therapies or chemotherapies) (Figure 2A,B).…”

Section: State-of-the Art Of Bispecific Antibodies In Solid Tumorsmentioning

confidence: 99%

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Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies

et al. 2021

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Solid tumors adopt multiple mechanisms to grow, evade immune responses, and to withstand therapeutic approaches. A major breakthrough in the armamentarium of anti-cancer agents has been the introduction of monoclonal antibodies (mAbs), able to inhibit aberrantly activated pathways and/or to unleash antigen (Ag)-specific immune responses. Nonetheless, mAb-mediated targeted pressure often fails due to escape mechanisms, mainly Ag loss/downregulation, ultimately providing therapy resistance. Hence, in order to target multiple Ag at the same time, and to facilitate cancer-immune cells interactions, bispecific antibodies (bsAbs) have been developed and are being tested in clinical trials, yielding variable safety/efficacy results based on target selection and their structure. While in hematologic cancers the bsAb blinatumomab recently reached the Food and Drug Administration (FDA)-approval for B Cell Acute Lymphoblastic Leukemia, bsAbs use in solid tumors faces considerable challenges, such as target Ag selection, biodistribution, and the presence of an immune-suppressive tumor microenvironment (TME). This review will focus on the state-of-the art, the design, and the exploitation of bsAbs against solid malignancies, delineating their mechanisms of action, major pitfalls, and future directions.

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Lung Cancer

Berchem,

Peters

2024

Side Effects of Cancer Therapy

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The promise of bispecific antibodies: Clinical applications and challenges

Cited by 36 publications

References 140 publications

Advances in Immunotherapy for Adult Glioblastoma

Advances in Immunotherapy for Adult Glioblastoma

Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies

Lung Cancer

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