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Simple Summary: Bispecific antibodies are a novel type of immune-based therapy used to treat patients with non-Hodgkin's lymphoma. This review article will help define the current treatment landscape of non-Hodgkin's lymphoma and detail ways in which bispecific antibodies fit in the current management paradigm, with special attention paid to diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. B-cell non-Hodgkin's lymphoma (NHL) refers to a heterogenous group of diseases, all of which have a wide range of treatment strategies and patient outcomes. There have been multiple novel, immune-based therapies approved in NHL in the last decade, including bispecific antibodies (BsAbs) and chimeric antigen receptor therapy (CAR-T). With a host of new therapies, an important next step will be determining how these therapies should be sequenced in contemporary management strategies. This review seeks to offer a framework for the ways in which BsABs can be incorporated into the current management paradigm for NHL, with special attention paid to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). [ABSTRACT FROM AUTHOR]

Non-Hodgkin lymphomas (NHLs) represent a diverse group of hematologic malignancies derived from various cells. B-cell NHLs represent the largest fraction of lymphomas diagnosed and treated in the United States. Standard chemo-immunotherapies with rituximab and multiagent cytotoxic regimens have proven to be effective in the management of these lymphoproliferative neoplasms; nonetheless, a considerable fraction of patients still experience relapse or have treatment-refractory disease. Therapeutic advances using novel immunotherapeutic agents as well as cell-based treatments, such as chimeric antigen receptor (CAR) T-cell therapies, have improved the outcomes of relapsed/refractory (R/R) B-cell NHL. Most of these new treatment strategies are not curative and most patients succumb to R/R disease, leaving this population with an unmet need for effective and well-tolerated therapeutic options. One of these up-and-coming options are bispecific antibodies (BsAb), either as single agent or in combination with other medications. Conclusion: BsAbs offer a novel "off the shelf" chemotherapy-free approach in the management of R/R B-cell NHL. Advancements in antibody construct design along with improved safety profile and clinical effectiveness of the most recent BsAbs suggest that these agents are a promising new option in the management of R/R B-cell NHL. [ABSTRACT FROM AUTHOR]

Background: In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients. Methods: PubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR). Results: Eleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively. Conclusions: In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that the detection and clearance of cancer cells via phagocytosis induced by innate immune checkpoints play significant roles in tumor-mediated immune escape. The most well-described innate immune checkpoints are the "don't eat me" signals, including the CD47/signal regulatory protein α axis (SIRPα), PD-1/PD-L1 axis, CD24/SIGLEC-10 axis, and MHC-I/LILRB1 axis. Molecules have been developed to block these pathways and enhance the phagocytic activity against tumors. Several clinical studies have investigated the safety and efficacy of CD47 blockades, either alone or in combination with existing therapy in hematological malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and lymphoma. However, only a minority of patients have significant responses to these treatments alone. Combining CD47 blockades with other treatment modalities are in clinical studies, with early results suggesting a synergistic therapeutic effect. Targeting macrophages with bispecific antibodies are being explored in blood cancer therapy. Furthermore, reprogramming of pro-tumor macrophages to anti-tumor macrophages, and CAR macrophages (CAR-M) demonstrate anti-tumor activities. In this review, we elucidated distinct types of macrophage-targeted strategies in hematological malignancies, from preclinical experiments to clinical trials, and outlined potential therapeutic approaches being developed. [ABSTRACT FROM AUTHOR]

Background: The bispecific antibody (bsAbs) research around the world has undergone great changes. We analyzed the global trend of bsAbs research and compared the differences in clinical research of bsAbs between China and worldwide. Methods: BsAbs research clinical trials information was retrieved through the online open-resource clinical trial registration platform. Research information including organizations, identity numbers, locations, phases, participating centers, conditions, status, enrollment, targets, spectrums of mechanism of action (MOA), and start date was collected. Clinical trials were divided into two categories based on the attributes of pharmaceutical companies (international or China-initiated or involved). Results: From 1997 to 2020, 272 clinical trials regarding bsAbs research were retrieved. Twenty-nine percent of the studies were contributed by companies from Chinese institutions, which followed the USA and ranked second. The clinical trials of bsAbs are mainly concentrated on phase I (n = 161), phase I/II (n = 54), and phase II (n = 51), and the number of phase III trials is still rare (n = 4). Tumor species distribution analysis shows that there are significantly higher focuses on gastric cancer (n = 18), esophageal/gastroesophageal junction cancer (n = 16), bladder cancer (n = 10), biliary malignant tumor (n = 8), nasopharyngeal cancer (n = 6), and thymic cancer (n = 2) in China. BsAbs target and spectrums of MOA analysis showed that international companies mainly focus on bsAbs with CD3-based (n = 63) target with MOA of T-cell redirection, while researches in China pay more attention to PD-1 (n = 9)/PD-L1 (n = 7) axises with MOA of double immune checkpoint blocking. Conclusion: Global bsAbs research increased rapidly during the 1997 to 2020 period. The developed countries in America and Europe are leading the trend of bsAbs research. Anticancer bsAbs clinical research in China is booming and chasing after the world trend. [ABSTRACT FROM AUTHOR]

Advanced follicular lymphoma (FL) often relapses after front-line chemoimmunotherapy, and many patients will eventually require subsequent therapy. In 2021, two new therapies were granted approval by the Food and Drug Administration (FDA), including the PI3Kδ inhibitor umbralisib and the chimeric antigen receptor–T-cell therapy (CAR-T) axicabtagene ciloleucel. Herein, we present the latest advances in the management of FL, discussing the recently approved therapies in the relapsed and refractory (R/R) setting and various new therapeutic modalities that have the potential to change the treatment landscape and natural history of R/R FL. [ABSTRACT FROM AUTHOR]

There are limited structural brain and retina alteration data from schizophrenia patients who experience visual disturbances (VDs) with or without auditory hallucinations (AHs). We compared brain and retina alterations between first-episode untreated schizophrenia patients with VDs (FUSCH-VDs) with versus without AHs, and between patients and healthy controls (HCs)(N = 30/group). VDs, AHs, gray matter volumes (GMVs), and retinal thicknesses were evaluated with the Bonn Scale for Assessment of Basic Symptoms (BSABS) scale, the Auditory Hallucinations Rating Scale (AHRS), magnetic resonance imaging (MRI), and optical coherence tomography (OCT), respectively. Compared to HCs, FUSCH-VDs had reduced GMVs, mainly in dorsal V3/V3A and V5 regions, the fusiform gyrus, and ventral V4 and V8 regions. Most FUSCH-VDs (85.0%; 51/60) had primary visual cortex-retina co-impairments. FUSCH-VDs with AHs had more serious and larger scope GMV reductions than FUSCH-VDs without AHs. FUSCH-VDs with AHs had significant retinal thickness reductions compared to HCs. Primary visual cortex-retina co-impairments were found to be more common, and more pronounced when present, in FUSCH-VDs with AHs than in FUSCH-VDs without AHs. The present findings support the notion that VDs and AHs may have reciprocal deteriorating actions in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established. More than 30 mature commercial technology platforms have been used to create and develop BsAbs based on the heterologous recombination of heavy chains and matching of light chains. The detailed mechanisms of clinical/therapeutic action have been demonstrated with these different types of BsAbs. Three kinds of BsAbs have received market approval, and more than 110 types of BsAbs are at various stages of clinical trials. In this paper, we elaborate on the classic platforms, mechanisms, and applications of BsAbs. We hope that this review can stimulate new ideas for the development of BsAbs and improve current clinical strategies. [ABSTRACT FROM AUTHOR]