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Bispecific antibodies in cancer immunotherapy.

ABSTRACT: Following the clinical success of immune checkpoint antibodies targeting CTLA-4, PD-1 or PD-L1 in cancer treatment, bispecific antibodies are now emerging as a growing class of immunotherapies with potential to further improve clinical efficacy and safety. We describe three classes of immunotherapeutic bispecific antibodies: (a) cytotoxic effector cell redirectors; (b) tumor-targeted immunomodulators; and (c) dual immunomodulators. Cytotoxic effector cell redirectors are dominated by T-cell redirecting compounds, bispecific compounds engaging a tumor-associated antigen and the T-cell receptor/CD3 complex, thereby redirecting T-cell cytotoxicity to malignant cells. This is the most established class of bispecific immunotherapies, with two compounds having reached the market and numerous compounds in clinical development. Tumor-targeted immunomodulators are bispecific compounds binding to a tumor-associated antigen and an immunomodulating receptor, such as CD40 or 4-1BB. Such compounds are usually designed to be inactive until binding the tumor antigen, thereby localizing immune stimulation to the tumor environment, while minimizing immune activation elsewhere. This is expected to induce powerful activation of tumor-specific T cells with reduced risk of immune-related adverse events. Finally, dual immunomodulators are bispecific compounds that bind two distinct immunomodulating targets, often combining targeting of PD-1 or PD-L1 with that of LAG-3 or TIM-3. The rationale is to induce superior tumor immunity compared to monospecific antibodies to the same targets. In this review, we describe each of these classes of bispecific antibodies, and present examples of compounds in development.

SUBMITTER: Dahlen E

PROVIDER: S-EPMC5933537 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Bispecific antibodies in cancer immunotherapy.

Dahlén Eva E Veitonmäki Niina N Norlén Per P

Therapeutic advances in vaccines and immunotherapy 20180201 1

Following the clinical success of immune checkpoint antibodies targeting CTLA-4, PD-1 or PD-L1 in cancer treatment, bispecific antibodies are now emerging as a growing class of immunotherapies with potential to further improve clinical efficacy and safety. We describe three classes of immunotherapeutic bispecific antibodies: (a) cytotoxic effector cell redirectors; (b) tumor-targeted immunomodulators; and (c) dual immunomodulators. Cytotoxic effector cell redirectors are dominated by T-cell redi ...[more]

PMID: 29998217

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Project description:BackgroundBispecific antibody (BsAb)-based cancer immunotherapy has provided new avenues for the treatment of various malignancies. The approval of Blinatumomab has encouraged further investigation into these treatments, and a series of preclinical and clinical trials have been conducted, together with the publication of numerous articles. Here, the knowledge structure of BsAb-based cancer immunotherapy is summarized using bibliometric analysis to provide in-depth insight into current research trends and foci.MethodsThe studies included in the bibliometric analysis of BsAbs in cancer immunotherapy were retrieved from the online Web of Science Core Collection (WOSCC) database on April 16th, 2023. Visualization analysis was performed with the help of CtieSpace (version 6.2.2.msi [64-bit]), VOSviewer (version 1.6.19), R (version 4.2.1), and the Bibliometric analysis platform (R-based online data processing tool).ResultsA total of 1750 papers were identified. Analysis of annual publications and total citations indicated that publications have increased steadily over the past few decades. The USA, followed by Germany, had largest number of publications, making significant contributions to the field. The Memorial Sloan Kettering Cancer Center received the highest number of citations (n = 3769). However, its collaboration and cooperation with different institutions require further strengthening. MAbs and Clinical Cancer Research published the most papers, while Blood and Cancer Research were the most commonly co-cited journals. DM Goldenberg from the USA published the most articles with the highest H-index (34), and the most co-cited author (2137 citations) was PA Baeuerle; both these authors have distinguished achievements in this field. Analysis of co-cited references and keywords showed that the hotspots and research focus on the use of BsAbs for solid tumors have increased rapidly while the application of BsAb immunotherapy in hematologic malignancies has expanded significantly. The hot topics in the field included cytokine release syndrome, the efficacy and safety of BsAbs, resistance mechanisms, and the exploration and optimization of combination therapies.ConclusionCancer immunotherapies based on BsAbs are a hot topic in research. Current studies focus on the construction and optimization of BsAb structure, as well as their combination with other treatment modalities to improve their efficacy and overcome resistance. Furthermore, it is expected that the ongoing investigation of BsAb-based immunotherapy for solid tumors will bear fruit with significant clinical application prospects in the near future.

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Bispecific antibodies in cancer immunotherapy.

Publications

Bispecific antibodies in cancer immunotherapy.

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