ADC Development Services Targeting CD19

In recent years, antibody-drug conjugates (ADCs) are proved as one of the most promising therapy for refractory cancer. As an experienced service provider in antibody and bio-conjugation field, Creative Biolabs has extensive expertise in the custom ADCs design and construction. Based on sophisticated equipments, advanced technologies and highly experienced staffs, Creative Biolabs provides a range of customized ADCs development service against the CD19 biomarker and our ADC service package includes ADC Antibody Screening, DrugLnk™ Custom Synthesis, Antibody Design and Conjugation, ADC in vitro Analysis and ADC in vivo Analysis, etc. Our goal is to provide you with the most affordable and high-quality service to ensure your satisfaction in a timely and professional manner.

Introduction of CD19

CD19, also known as B4 or CVID3, is a type of I transmembrane glycoprotein encoded by the cd19 gene that located on the short arm of chromosome 16. It is a member of the immunoglobulin (Ig) superfamily and composed of a single transmembrane domain, a cytoplasmic C-terminus, and extracellular N-terminus. CD19 is mainly expressed on normal and neoplastic B cells, as well as follicular dendritic cells. It plays a role in the establishing of intrinsic B cell signaling thresholds via regulating both B cell receptor (BCR)-dependent and independent signaling. It also functions in the immunoglobulin-induced activation of B cells. Furthermore, CD19 interacts with various protein kinases to induce an optimal immune response. Besides, it has been found involved in the MHC class II-mediated signaling.

Continuous signaling of CD79b and CD19 is required for the fitness of lymphoma B cells. Fig.1 Continuous signaling of CD79b and CD19 is required for the fitness of lymphoma B cells.

Anti-CD19 ADC for Non-Hodgkin Lymphoma (NHL)

CD19 is a potential target used in targeted immunotherapy because it is a B-cell-specific biomarker expressed in the vast majority of patients with B-cell NHL. Denintuzumab mafodotin (also known as SGN-CD19A) is a novel antibody-drug conjugate consisting of a humanized anti-CD19 monoclonal antibody attached to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a maleimidocaproyl linker. Phase I study showed that SGN-CD19A has significant antitumor activity in patients with relapsed/refactory B-NHL and well-tolerated, low rates of myelosuppression and peripheral neuropathy.

SGN-CD19B is another ADC against the CD19, which is composed of an anti-CD19 humanized antibody (hBU12ec) linked to a DNA-cross linking pyrrolobenzodiazepine (PBD) dimer drug (SGD-1882) via a protease-cleavable linker. Preclinical trials showed that the ADC has potent anti-B-cell malignancies activity. SGN-CD19B can be rapidly internalized once binding to CD19, then release the PDB drug. Subsequently, the drug causes the tumor cells apoptosis and death. Currently, the therapeutic potential of SGN-CD19B in relapsed/refractory B-NHL is investigated in the phase 1 clinical trial.

Tumor regressions of SGN-CD19B. Fig.2 Tumor regressions of SGN-CD19B. (Ryan, 2017)

Anti-CD19 ADC for Diffuse Large B-cell Lymphoma (DLBCL)

Coltuximab ravtansine (also known as SAR3419) is a novel ADC composed of an anti-CD19 monoclonal antibody and a potent cytotoxic maytansinoid, DM4, via a disulfide bond linker. The antibody specifically combines with the CD19 target and leads to the internalization of the antibody-drug complex and intracellular release of DM4. DM4 serves as a type of potent tubulin polymerization and microtubule assembly inhibitor, and it can perform the killing of cancer cells. Besides, Phase II study has been investigated in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. Clinical results demonstrated that SAR3419 presents well-tolerated and moderate clinical responses in pretreated patients with relapsed/refractory DLBCL.

Anti-CD19 ADC for Acute Lymphoblastic Leukemia (ALL)

ADCT-402 (loncastuximab tesirine) is an ADC composed of an anti-CD19 humanized antibody linked to the pyrrolobenzodiazepine (PBD) dimer cytotoxin via a valine-alanine cleavable, maleimide linker. Preclinical studies showed that the ADCT-402 has potent anti-tumor activity in mouse models of B-ALL. In the Phase I study, ADCT-402 presented well-tolerated and complete remissions in patients with R/R B-ALL.

What Can We Do for You?

Creative Biolabs provides comprehensive ADCs preparation services targeting the CD19, including the production of specific antibody and high-quality linker-payload as well as the bioconjugation. As the leader of drug discovery, we are confident to provide flexible and reliable services to accelerate your research. Contact us for a free consultation with the scientific team and discover how Creative Biolabs can be a valuable resource and partner for your organization.

Reference

  1. Ryan, M. C.; et al. Therapeutic potential of SGN-CD19B, a PBD-based anti-CD19 drug conjugate, for treatment of B-cell malignancies. Blood. 2017, 130(18): 2018-2026.

For lab research use only, not for any in vivo human use.


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