CD22 is a multifunctional receptor that regulates B lymphocyte survival and signal transduction. Being CD22 a B-cell-specific transmembrane protein involved in B cell activation, it is mainly expressed on mature B lymphocytes and acute lymphoblastic leukemia (ALL). BOC Sciences can provide customers with highly customized and high-level antibody-drug conjugation (ADC) discovery services. Up to now, our R&D team has successfully developed and improved dozens of ADCs. In addition to development services, we also provide ADC manufacturing process development and production services to save time and accelerate the commercialization process.
The antigen CD22 is a transmembrane glycoprotein expressed on mature B-cells and on up to 90% of B-blasts, but not on other non-B lineages including haematopoietic stem cells. Therefore, CD22-targeted treatment is not expected to affect other tissues. lts function is unclear; however, recent studies suggest that it regulates B-cell functions via B-cell receptor (BCR) activation, has an impact on their survival, and serves as an adhesion molecule. In vivo animal studies demonstrated that combined therapy with epratuzumab and rituximab was more effective in controlling lymphoma growth and prolonging survival than either the agent alone. The effect in systemic lupus erythematosus (SLE) is exerted via CD22 binding, resulting in modulation and inhibition of B-cell proliferation.
Fig. 1. CD22 and siglec-G structure and expression (Trends in Immunology August. 2012, 33(8): 413-420).
ln August 2017, the FDA granted approval for inotuzumab ozogamicin (an ADC chemotherapeutic drugs) for the treatment of adult patients with relapsed or refractory B-cell precursor ALL, currently being the only anti-CD22 agent approved for clinical use. Inotuzumab ozogamicin is a humanized anti-CD22 lgG4 monoclonal antibody covalently linked via an acid-labile linker with the antitumor antibiotic calicheamicin. Upon binding of this compound to CD22 on the B-cell surface, the cytotoxic agent is released intracellularly and induces DNA strand cleavage, with the subsequent cell death mediated through calicheamicin-induced apoptosis and not by CD22 signalling.
ALL is a malignant hematologic tumor with highly aggressive characteristics, which is prone to relapse, has a poor prognosis and few clinically effective drugs. Approximately 40% of annual ALL cases occur in adults, yet estimated 5-year overall survival rates are about 40% to 50% in adults (and vary broadly by age) compared with 90% in children. Studies suggest that CD22 is expressed in 100% of ALL cases, with 95% expressed in ≥ 90% of blasts. BOC Sciences has built a world-class ADC technology platform, providing one-stop services for CD22-targeted ADC therapy in ALL. We have many years of rich experience and provide good technical support for ADC development and GMP production.
NHLs are a diverse group of malignancies arising from lymphocytes. They are the seventh leading type of cancer, accounting for approximately 4% to 5% of new cancer cases and 3% to 4% of cancer-related deaths. B cell NHL can be broadly divided into low-grade (histologically indolent) and high-grade (histologically aggressive) subtypes. Low-grade B cell NHLs usually grow relatively slowly and may not need immediate treatment. High-grade B cell NHLs usually grow relatively quickly and can be rapidly fatal if left untreated; with prompt treatment, however, they are often curable. The restricted lineage of CD22 and rapid internalization upon antibody binding make CD22 an appealing target for an ADC therapeutic for B cell malignancies. With the professional ADC design engineer team, BOC Sciences can skillfully complete ADC construction, including custom development services for specific targets and tumors. We strictly control the process parameters and fully in accordance with the process to ensure product quality.
Fig. 2. Non-hodgkin lymphoma (NHL) cells.
CML is an indolent malignant hematological disease that accounts for about 15% of all cases of leukemia. This disorder results from the formation of the Philadelphia chromosome that involves a reciprocal translocation that produces a lengthened chromosome 9 and shortened chromosome 22- the Philadelphia chromosome. As a consequence of the translocation, the dysregulated BCR-Abl fusion oncoprotein is formed and it produces the abnormal proliferation of white blood cells. CD22 is a B cell-restricted surface protein that modulates BCR signal transduction in mature B cells. As a leader in ADC development and manufacturing, BOC Sciences has multiple complex processes and high volume production capabilities. We have the ability to customize target screening and corresponding ADC development services for customers. We aim to help our clients develop simplified and controlled manufacturing processes to win the ADC R&D track.
DLBCL is an aggressive malignancy that has been traditionally treated with anthracycline-based chemotherapy, but approximately one-third of patients relapse after first-line therapy or have primary refractoriness. DLBCL originates from mature B cells and has been historically classified into germinal center B cell DLBCL or activated B cell DLBCL based on the cell of origin. The disease frequently presents with many genetic alterations, some of which are commonly found in other subtypes of NHL, and it can also originate from the transformation of low-grade B cell lymphoma. DLBCL is typically treated with chemoimmunotherapy, such as in the form of ADC which consists of antibody, payload, and linker. As a professional one-stop ADC development service platform, scientists from BOC Sciences are committed to providing CD22-targeted ADC therapy for DLBCL to customers worldwide.
Leveraging advanced antibody screening technology and genetic engineering technology, BOC Sciences provides a wide range of indication screening services for ADC therapy, including various solid tumors and infections, autoimmunity, and metabolic diseases. Our comprehensive ADCs system offers a wide range of ADCs design and construction services against the CD22-targeted therapy, including acute lymphoblastic leukemia, non-hodgkin lymphoma, chronic myelogenous leukemia and diffuse large B-cell lymphoma ect. Our services will assist customers in candidate selection and optimization in different phases of ADCs drug development. Our process technology is designed to improve the specificity and stability of ADC drugs, thereby improving the safety factor. Currently, our custom development services include antibody modification and conjugation, payload development and linker development.
Scientists from BOC Sciences provide a full suite of development services for client's research targets or oncology indications. Our services cover antibody modification, bioconjugation, small molecule synthesis, cGMP manufacturing and multiple analytical characterization support services.