Bispecific antibody

T cell-based immunotherapies for solid tumors have not achieved the clinical success observed in hematological malignancies, partially due to the immunosuppressive effect promoted by the tumor microenvironment, where PD-L1 and TGF-β play a pivotal role. However, durable responses to immune checkpoint inhibitors remain limited to a minority of patients, while TGF-β inhibitors have not reached the market yet. Here, we describe a bispecific antibody for dual blockade of PD-L1 and TFG-β, termed AxF (scFv)2 , under the premise that combination with T cell redirecting strategies would improve clinical benefit...

BACKGROUND: Cancer immunotherapy including immune checkpoint inhibitors is only effective for a limited population of patients with cancer. Therefore, the development of novel cancer immunotherapy is anticipated. In preliminary studies, we demonstrated that tetracyclines enhanced T-cell responses. Therefore, we herein investigated the efficacy of tetracyclines on antitumor T-cell responses by human peripheral T cells, murine models, and the lung tumor tissues of patients with non-small cell lung cancer (NSCLC), with a focus on signaling pathways in T cells...

Outcomes for relapsed/refractory multiple myeloma (RRMM) patients have dramatically improved following the development and now growing utilization of B cell maturation antigen targeted chimeric antigen receptor (CAR) T cell therapy and bispecific antibody (BsAb) therapy. However, healthcare utilization as a quality-of-life metric in these growing populations has not been thoroughly evaluated. We performed a retrospective cohort study evaluating the frequency and cause of unscheduled healthcare interactions (UHIs) among RRMM patients responding to B-cell maturation antigen targeted BsAbs and CAR T cell therapies (N = 46)...

Phage display technology has become an important research tool in biological research, fundamentally changing the traditional monoclonal antibody preparation process, and has been widely used in the establishment of antigen-antibody libraries, drug design, vaccine research, pathogen detection, gene therapy, antigenic epitope research, and cellular signal transduction research.The phage display is a powerful platform for technology development. Using phage display technology, single chain fragment variable (scFv) can be screened, replacing the disadvantage of the large size of traditional antibodies...

In calendar year 2023, the United States Food and Drug Administration (US FDA) approved a total of 55 new molecular entities, of which 12 were in the class of therapeutic antibodies. Besides antibody protein drugs, the US FDA also approved another five non-antibody protein drugs, making the broader class of protein drugs about 31% of the total approved drugs. Among the 12 therapeutic antibodies approved by the US FDA, 8 were relatively standard IgG formats, 3 were bivalent, bispecific antibodies and 1 was a trivalent, bispecific antibody...

INTRODUCTION: The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing, particularly among younger populations. It is projected that the number of new cases will increase by almost 50% by 2040, with market revenues expected to triple in the same period. Despite the recent introduction of immune checkpoint inhibitors (ICIs) into the therapeutic armamentarium, the vast majority of patients with recurrent and/or metastatic (R/M) HNSCC fail to derive durable benefits from systemic therapy...

BACKGROUND: Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment...

Despite the development of various therapeutic agents, multiple myeloma remains incurable. Recently, T-cell redirected immunotherapy has become a promising strategy for the treatment of refractory myeloma. Clinical trials using chimeric antigen receptor (CAR)-T cells and bispecific antibodies have demonstrated successful anti-myeloma responses in triple-class-refractory patients. However, unique and unwanted immune effects associated with on-target/off-target reactivity of activated immune cells need to be considered and properly managed...

Cancer stem cells (CSCs) represent a subpopulation within tumors that promote cancer progression, metastasis, and recurrence due to their self-renewal capacity and resistance to conventional therapies. CSC-specific markers and signaling pathways highly active in CSCs have emerged as a promising strategy for improving patient outcomes. This review provides a comprehensive overview of the therapeutic targets associated with CSCs of solid tumors across various cancer types, including key molecular markers aldehyde dehydrogenases, CD44, epithelial cellular adhesion molecule, and CD133 and signaling pathways such as Wnt/β-catenin, Notch, and Sonic Hedgehog...

Enterotoxigenic Escherichia coli (ETEC) strains are significant contributors to postweaning diarrhea in piglets. Of the ETEC causing diarrhea, K88 and F18 accounted for 92.7%. Despite the prevalence of ETEC K88 and F18, there is currently no effective vaccine available due to the diversity of these strains. This study presents an innovative approach by isolating chicken-derived single-chain variable fragment antibodies (scFvs) specific to K88 and F18 fimbrial antigens from chickens immunized against these ETEC virulence factors...

Uncommon (ucEGFRmuts) and rare epidermal growth factor receptor ( EGFR ) mutations account for 10-15% of diagnosed cases and consist of a heterogeneous group represented by several clusters within exons 18-21 (e.g., exon 18 point mutations, exon 21 L861X, exon 20 S768I), as well as exon 20 insertions (Ex20ins). Their incidence is under molecular and clinical investigation following recent findings that reported an increase of sensitivity and specificity of next-generation sequencing (NGS) methods. Consequently, their detection allows for the selection of emerging treatment options to significantly improve patients' outcomes in these particular subgroups of EGFR -mutated advanced non-small cell lung cancer (NSCLC)...

In the last few years, several agents targeting molecules that sustain the survival and the proliferation of chronic lymphocytic leukemia (CLL) cells have become clinically available. Most of these drugs target surface proteins, such as CD19 or CD20, via monoclonal or bispecific monoclonal antibodies (BsAbs), CAR T cells, intracellular proteins like BTK by using covalent or non-covalent inhibitors or BCL2 with first or second generation BH3-mimetics. Since the management of CLL is evolving quickly, in this review we highlighted the most important innovative treatments including novel double and triple combination therapies, CAR T cells and BsAbs for CLL...

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of lymphoma, comprising heterogeneous patient subgroups with distinctive biological and clinical characteristics. The R-CHOP combination (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard initial treatment, yielding prolonged remissions in over 60% of patients with advanced-stage disease. Several attempts to enhance the outcomes of this regimen over the last two decades have shown limited success. Various novel therapeutic approaches have recently emerged in lymphoma, demonstrating promising results...

Improvement in the therapeutics for multiple myeloma (MM) has been continuously developed owing to the application of novel drugs and technologies in the last 20 years. The standard first-line therapy for MM consists of a three-drug induction regimen based on immunomodulatory drugs and proteasome inhibitors combined with autologous stem cell transplantation. However, MM remains incurable; therefore, therapies for relapsed/refractory MM (RRMM) are emerging and evolving rapidly. This study aimed to summarize and review the results of RRMM trials over the past 5 years to provide a holistic overview and insights for practitioners in related fields and to provide additional ideas for clinical trialists...

INTRODUCTION: The prognosis of multiple myeloma (MM) continues to improve. Recent progress in therapies, using immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies, has greatly improved patients' outcomes. Despite these advancements, relapses still happen often, and patients can become resistant to the usual treatments. Newer treatments, such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs) targeting B-cell maturation antigen (BCMA), have resulted in excellent outcomes in patients with limited treatment options...

INTRODUCTION: The therapeutic potential of bispecific antibodies is becoming widely recognised, with over a hundred formats already described. For many applications, enhanced tissue penetration is sought, so bispecifics with low molecular weight may offer a route to enhanced potency. Here we report the design of bi- and tri-specific antibody-based constructs with molecular weights as low as 14.5 and 22 kDa respectively. METHODS: Autonomous bovine ultra-long CDR H3 (knob domain peptide) modules have been engineered with artificial coiled-coil stalks derived from Sin Nombre orthohantavirus nucleocapsid protein and human Beclin-1, and joined in series to produce bi- and tri-specific antibody-based constructs with exceptionally low molecular weights...

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2...

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Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death...

Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation. Here, we explore a bsAb strategy for generation of pan-ebolavirus and pan-filovirus immunotherapeutics...