Hematology pertains to the domain of medical science concerned with disorders impacting the production of blood components or disrupting the blood coagulation process. Within this field, conditions encompass a range of maladies, including blood cancers such as leukemia, myeloma, and lymphoma, bleeding disorders exemplified by hemophilia, and blood clotting disorders. Hematological research frequently intersects with oncology, often sharing similar therapeutic approaches.
Creative Biolabs offers a comprehensive suite of services for bispecific antibodies (BsAbs) that covers the entire spectrum—from design and engineering to manufacturing and rigorous analysis. Our specialized BsAbs are tailored for hematology applications, addressing a wide range of uses, including the treatment of various blood cancers such as acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia (B cell ALL), chronic lymphocytic leukemia (CLL), and hemophilia.
Fig.1 Quantitative analysis of CD33-CD3 BsAb released from cryogel-encapsulated MSCs.1
BsAbs possess the unique ability to simultaneously bind two ligands/antigens, instigating cascading reactions within specific signaling pathways. Factor VIII (FVIII), also recognized as anti-hemophilic factor (AHF), plays a pivotal role as a vital blood-clotting protein coursing through the bloodstream. In response to injury, the active variant of this protein, Coagulation factor VIIIa, engages with Factor IXa and Factor X, setting in motion the coagulation cascade. This intricate interaction ultimately activates Factor X, instigating a sequence of events culminating in blood clot formation. However, individuals afflicted with the bleeding disorder hemophilia A suffer from an absence of coagulation factor VIIIa. For example, a reported KIH BsAb crafted to bridge Factor IXa and Factor X. This BsAb faithfully emulates the function of coagulation factor VIIIa in healthy individuals, thereby triggering the downstream signaling pathways. Notably, the Fc region of this BsAb confers a protracted serum half-life, enhancing its therapeutic efficacy.
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Data 1: Redirecting T cells to hematological malignancies with bispecific antibodies The interest in the BsAb field has spawned a wealth of preclinical and clinical investigations, encompassing not only B-cell-derived lymphoblastic leukemia and lymphoma but also acute myeloid leukemia and multiple myeloma. In this review, we will delve into the achievements and hurdles surrounding T-cell-targeted BsAbs in the context of immunotherapy for hematological malignancies. Particular emphasis will be placed on an examination of clinical studies and the exploration of strategies aimed at augmenting their therapeutic efficacy. This investigation has yielded a BsAb aimed at the dual targeting of VEGF and DLL4, representing a novel anti-angiogenic cancer therapeutic. The BsAb not only amplifies the impact of VEGF inhibitors but also holds the potential to surmount resistance encountered in anti-VEGF therapy.
Fig.2 Selected BsAb formats.2 |
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Data 2: Bispecific antibodies in hematological malignancies: a scoping review BsAbs have changed a paradigm shift in the therapeutic landscape for advanced hematological malignancies. Several approved BsAbs have demonstrated notable efficacy and safety profiles. Furthermore, early-phase clinical trials investigating a multitude of other BsAbs have unveiled promising anti-neoplastic activity. However, it is imperative to delve deeper into the efficacy and tolerability of select BsAbs. Antigen escape stands out as a pivotal resistance mechanism against BsAb therapy. To counteract this challenge, there is a pressing need to decipher additional tumor-associated target antigens and explore the potential of combinatorial, multi-antigenic BsAbs. Additionally, the immunosuppressive tumor microenvironment (TME) prevalent in hematological malignancies remains a substantial obstacle to the effectiveness of BsAbs. Thus, investigating strategies to normalize the TME, such as the utilization of immune checkpoint inhibitors and immunomodulatory agents, offers a promising avenue to enhance the therapeutic potential of BsAbs while mitigating resistance.
Fig. 3 BsAb for the therapeutic intervention of acute myelogenous leukemia.3 |
Creative Biolabs, with its comprehensive antibody engineering and production platforms and an unparalleled team of researchers, ensures the delivery of highly satisfactory, time-efficient, and cost-effective BsAb services to our valued clients. Our commitment to assisting your endeavors in the realms of science and medicine remains unwavering. Please don't hesitate to contact us for details.
References
1. Aliperta, Roberta, et al. "Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy." Scientific Reports 7.1 (2017): 42855.
2. Velasquez, Mireya Paulina, Challice L. Bonifant, and Stephen Gottschalk. "Redirecting T cells to hematological malignancies with bispecific antibodies." Blood, The Journal of the American Society of Hematology 131.1 (2018): 30-38.
3. Omer, Mohamed H., et al. "Bispecific antibodies in hematological malignancies: a scoping review." Cancers 15.18 (2023): 4550.
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