Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.

ABSTRACT: In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

SUBMITTER: Sun Y

PROVIDER: S-EPMC10501874 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.

Sun Yanze Y Yu Xinmiao X Wang Xiao X Yuan Kai K Wang Gefei G Hu Lingrong L Zhang Guoyu G Pei Wenli W Wang Liping L Sun Chengliang C Yang Peng P

Acta pharmaceutica Sinica. B 20230523 9

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selectio ...[more]

PMID: 37719370

Similar Datasets

Cancer therapy with bispecific antibodies: Clinical experience.

Project description:The binding of at least two molecular targets simultaneously with a single bispecific antibody is an attractive concept. The use of bispecific antibodies as possible therapeutic agents for cancer treatment was proposed in the mid-1980s. The design and production of bispecific antibodies using antibody- and/or receptor-based platform technology has improved significantly with advances in the knowledge of molecular manipulations, protein engineering techniques, and the expression of antigens and receptors on healthy and malignant cells. The common strategy for making bispecific antibodies involves combining the variable domains of the desired mAbs into a single bispecific structure. Many different formats of bispecific antibodies have been generated within the research field of bispecific immunotherapeutics, including the chemical heteroconjugation of two complete molecules or fragments of mAbs, quadromas, F(ab')2, diabodies, tandem diabodies and single-chain antibodies. This review describes key modifications in the development of bispecific antibodies that can improve their efficacy and stability, and provides a clinical perspective on the application of bispecific antibodies for the treatment of solid and liquid tumors, including the promises and research limitations of this approach.

| S-EPMC3785321 | biostudies-literature

Targeting T cells with bispecific antibodies for cancer therapy.

Project description:Bispecific antibodies (BiAbs) offer a unique opportunity to redirect immune effector cells to kill cancer cells. BiAbs combine the benefits of different binding specificities of two monoclonal antibodies (mAbs) into a single construct. This unique feature of BiAbs enables approaches that are not possible with single mAbs. Advances in antibody engineering and antigen profiling of malignant cells have led to the development of a number of BiAb formats and their combinations for redirecting effector cells to tumor targets. There have been significant advances in the design and application of BiAbs for intravenous and local injection.The initial barrier of cytokine storm has been partially overcome by more recent constructs that have improved clinical effectiveness without dose-limiting toxicities. Since the recent revival of BiAbs, there has been multiple, ongoing, phase I/II and III trials, and some promising clinical outcomes have been reported in completed clinical studies. This review focuses on arming T cells with BiAbs to create the 'poor man's cytotoxic lymphocyte'.

| S-EPMC3792709 | biostudies-other

Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy.

Project description:Advances in antibody engineering have led to the generation of more innovative antibody drugs, such as bispecific antibodies (bsAbs). Following the success associated with blinatumomab, bsAbs have attracted enormous interest in the field of cancer immunotherapy. By specifically targeting two different antigens, bsAbs reduce the distance between tumor and immune cells, thereby enhancing tumor killing directly. There are several mechanisms of action upon which bsAbs have been exploited. Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bsAbs targeting immunomodulatory checkpoints. Cadonilimab (PD-1 × CTLA-4) is the first approved bsAb targeting dual inhibitory checkpoints, which confirms the feasibility of bsAbs in immunotherapy. In this review we analyzed the mechanisms by which bsAbs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.

| S-EPMC10038071 | biostudies-literature

Bispecific antibodies: design, therapy, perspectives.

Project description:Antibodies (Abs) containing two different antigen-binding sites in one molecule are called bispecific. Bispecific Abs (BsAbs) were first described in the 1960s, the first monoclonal BsAbs were generated in the 1980s by hybridoma technology, and the first article describing the therapeutic use of BsAbs was published in 1992, but the number of papers devoted to BsAbs has increased significantly in the last 10 years. Particular interest in BsAbs is due to their therapeutic use. In the last decade, two BsAbs - catumaxomab in 2009 and blinatumomab in 2014, were approved for therapeutic use. Papers published in recent years have been devoted to various methods of BsAb generation by genetic engineering and chemical conjugation, and describe preclinical and clinical trials of these drugs in a variety of diseases. This review considers diverse BsAb-production methods, describes features of therapeutic BsAbs approved for medical use, and summarizes the prospects of practical application of promising new BsAbs.

| S-EPMC5784585 | biostudies-literature

Dual-target Bridging ELISA for Bispecific Antibodies.

Project description:Bispecific antibodies (BsAbs) are typically monoclonal antibody (mAb)-derived molecular entities engineered to bind to two distinct targets, including two antigens or two epitopes on the same antigen. When compared to parental monoclonal antibodies or combinational therapies, the generated BsAbs have the ability to bridge the two targets and thus may offer additional clinical benefits. Characterizing BsAbs' ability to bind to both targets simultaneously is critical for their biotherapeutic development. A range of bi-functional quantitative bridging assays to enable target-specific capture and detection of binding properties include enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), and cell-based flow cytometry. Developing suitable and robust cell-based bioassays is more challenging than non-cell-based binding assays because cell-based assays with complex matrices can be inherently variable and often lack precision. Compared to SPR, ELISA has a rapid setup and readily available method, being widely and extensively applied in almost every laboratory. Here, we describe a dual-target bridging ELISA assay that characterizes the ability of a HER2(human epidermal growth factor receptor 2)/PD-L1(programmed cell death ligand 1) BsAb in binding to both HER2 and PD-L1 simultaneously, a prerequisite for its envisioned mode of action. Graphical abstract.

| S-EPMC9548515 | biostudies-literature

Design and selection of optimal ErbB-targeting bispecific antibodies in pancreatic cancer.

Project description:The ErbB family of receptor tyrosine kinases is a primary target for small molecules and antibodies for pancreatic cancer treatment. Nonetheless, the current treatments for this tumor are not optimal due to lack of efficacy, resistance, or toxicity. Here, using the novel BiXAb™ tetravalent format platform, we generated bispecific antibodies against EGFR, HER2, or HER3 by considering rational epitope combinations. We then screened these bispecific antibodies and compared them with the parental single antibodies and antibody pair combinations. The screen readouts included measuring binding to the cognate receptors (mono and bispecificity), intracellular phosphorylation signaling, cell proliferation, apoptosis and receptor expression, and also immune system engagement assays (antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity). Among the 30 BiXAbs™ tested, we selected 3Patri-1Cetu-Fc, 3Patri-1Matu-Fc and 3Patri-2Trastu-Fc as lead candidates. The in vivo testing of these three highly efficient bispecific antibodies against EGFR and HER2 or HER3 in pre-clinical mouse models of pancreatic cancer showed deep antibody penetration in these dense tumors and robust tumor growth reduction. Application of such semi-rational/semi-empirical approach, which includes various immunological assays to compare pre-selected antibodies and their combinations with bispecific antibodies, represents the first attempt to identify potent bispecific antibodies against ErbB family members in pancreatic cancer.

| S-EPMC10157173 | biostudies-literature

Bispecific antibodies targeting dual tumor-associated antigens in cancer therapy.

Project description:PURPOSE:Bispecific antibodies (BsAbs) have emerged as a leading drug class for cancer therapy and are becoming increasingly of interest for therapeutic applications. As of April 2020, over 123 BsAbs are under clinical evaluation for use in oncology (including the two marketed BsAbs Blinatumomab and Catumaxomab). The majority (82 of 123) of BsAbs under clinical evaluation can be categorized as bispecific immune cell engager whereas a second less well-discussed subclass of BsAbs targets two tumor-associated antigens (TAAs). In this review, we summarize the clinical development of dual TAAs targeting BsAbs and provide an overview of critical considerations when designing dual TAA targeting BsAbs. METHODS:Herein the relevant literature and clinical trials published in English until April 1st 2020 were searched using PubMed and ClinicalTrials.gov database. BsAbs were considered to be active in clinic if their clinical trials were not terminated, withdrawn or completed before 2018 without reporting results. Data missed by searching ClinicalTrials.gov was manually curated. RESULTS:Dual TAAs targeting BsAbs offer several advantages including increased tumor selectivity, potential to concurrently modulate two functional pathways in the tumor cell and may yield improved payload delivery. CONCLUSIONS:Dual TAAs targeting BsAbs represent a valuable class of biologics and early stage clinical studies have demonstrated promising anti-tumor efficacy in both hematologic malignancies and solid tumors.

| S-EPMC7679314 | biostudies-literature

Bispecific Antibodies in Prostate Cancer Therapy: Current Status and Perspectives.

Project description:Prostate carcinoma (PC) is the second most common cancer in men. When the disease becomes unresponsive to androgen deprivation therapy, the remaining treatment options are of limited benefit. Despite intense efforts, none of the T cell-based immunotherapeutic strategies that meanwhile have become a cornerstone for treatment of other malignancies is established in PC. This refers to immune checkpoint inhibition (CI), which generally reinforces T cell immunity as well as chimeric antigen receptor T (CAR-T) cells and bispecific antibodies (bsAbs) that stimulate the T cell receptor/CD3-complex and mobilize T cells in a targeted manner. In general, compared to CAR-T cells, bsAb would have the advantage of being an "off the shelf" reagent associated with less preparative effort, but at present, despite enormous efforts, neither CAR-T cells nor bsAbs are successful in solid tumors. Here, we focus on the various bispecific constructs that are presently in development for treatment of PC, and discuss underlying concepts and the state of clinical evaluation as well as future perspectives.

| S-EPMC7867165 | biostudies-literature

Bispecific Antibodies and Antibody-Drug Conjugates for Cancer Therapy: Technological Considerations.

Project description:The ability of monoclonal antibodies to specifically bind a target antigen and neutralize or stimulate its activity is the basis for the rapid growth and development of the therapeutic antibody field. In recent years, traditional immunoglobulin antibodies have been further engineered for better efficacy and safety, and technological developments in the field enabled the design and production of engineered antibodies capable of mediating therapeutic functions hitherto unattainable by conventional antibody formats. Representative of this newer generation of therapeutic antibody formats are bispecific antibodies and antibody-drug conjugates, each with several approved drugs and dozens more in the clinical development phase. In this review, the technological principles and challenges of bispecific antibodies and antibody-drug conjugates are discussed, with emphasis on clinically validated formats but also including recent developments in the fields, many of which are expected to significantly augment the current therapeutic arsenal against cancer and other diseases with unmet medical needs.

| S-EPMC7175114 | biostudies-literature

Bispecific antibodies in cancer immunotherapy.

Project description: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.

| S-EPMC5933537 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data