ADC Development for CD30 Targets

ADC Development for CD30 Targets

CD30, a member of tumor necrosis factor, is highly expressed in specific cancers with limited expression in healthy tissues, thus making it an ideal therapeutic target. BOC Sciences is a biotech company dedicated to providing integrated antibody-drug conjugate (ADC) development services to customers. We intend to realize the full potential of your ADC candidate drugs through our first-class technical platform and mature experience. Currently, BOC Sciences provides ADC preparation services for various biomarkers for solid tumor treatment with its core advantages in high-quality antibody screening, pharmacochemistry and bioconjugation.

Introduction of CD30 Targets

A member of the tumor necrosis factor (TNF)/nerve growth factor receptor superfamily, CD30 is a 120-kDa transmembrane glycoprotein that has been long used as a marker for the Reed-Sternberg cells in Hodgkin lymphoma (HL). In addition, CD30 antigen was also found on activated T-, and B-cells and on activated and differentiated macrophages. It is constitutively expressed on viral-transformed B- and T-cells and transiently on mitogen-activated T-cells. The precise biological functions of this molecule remain to be fully elucidated, although it has been implied in the regulation of the balance between Th1 and Th2 responses and in the generation of memory and effector T-cells. Therefore, CD30-targeted agents may affect antibody-dependent cell-mediated cytotoxicity (ADCC) and exert a deleterious impact on humoral immunity.

Lymphoma cells. Fig. 1. Lymphoma cells.

Clinical ADC Therapy Targeting CD30

CD30 is an established therapeutic target in patients with HL and anaplastic large-cell lymphoma (ALCL). For example, brentuximab vedotin was the first ADC approved by the FDA for the treatment of relapsed/refractory HL and ALCL. Brentuximab vedotin is composed of a human/murine chimeric anti-CD30 lgG1 monoclonal antibody conjugated via a protease-cleavable linker with the microtubule disrupting agent monomethyl auristatin E (MMAE). Mechanistically, upon binding to CD30-expressing neoplastic cells, the ADC is internalized by endocytosis. Then, lysosomal degradation causes selective cleavage of the linker, allowing release of the MMAE. The MMAE molecules bind to tubulin, effectively disrupting the microtubule network with resultant cell cycle arrest and apoptosis.

ADC technology for CD30-positive lymphoma Fig. 2. ADC technology for CD30-positive lymphoma (Bioconjugate Chem. 2021, 32(3): 595-606).

Additionally, F0002-ADC is an investigational ADC, which interacts with the same target antigen of brentuximab vedotin, designed to improve the safety of the latter ADC by enhancing the linker stability and changing the payload. It consists of the anti-CD30 mAb cAC10, chemically conjugated with another antimitotic agent, a semi-synthetic derivative of the ansamycin antibiotic maytansine or mertansine, through the stable linker succinimidyl trans-4-(maleimidylmethyl) cyclohexane-1-carboxylate (SMCC).

Our CD30-targeted ADC Development Services (Include but are not limited to the followings)

CD30 Targeted Therapy in Anaplastic Large Cell Lymphoma (ALCL)

ALCL represents a heterogeneous group of T-cell non-Hodgkin lymphoma (NHL) mainly affecting children and young adults. It can present at both nodal and extranodal sites, the latter including skin, lung, liver, soft tissue and bone. Histopathologically, it is a heterogeneous disease with a number of morphological variant forms including small cell, lymphohistiocytic, Hodgkin-like and common forms. Immunophenotypic characterization of human ALCL revealed highly CD30-positive cells of T- or Null-Cell-origin and resulted in promising clinical trials with CD30-coupled antibodies. Thence, CD30 is an established therapeutic target of the CD30-targeting ADC in patients with ALCL.

CD30 Targeted Therapy in Primary Effusion Lymphoma (PEL)

PEL is an aggressive and rare malignancy predominantly occurring in patients with HIV infection and severe immunodeficiency. PEL has also been reported in recipients of solid organ transplants and in elderly patients in the absence of immunodeficiencies. PEL is a distinct subtype of B-cell NHL characterized by lymphomatous effusions within major body cavities (pleural, peritoneal, and pericardial); extracavitary tumors are rare but have been reported and have similar morphologic and phenotypic characteristics. Morphologically, PEL cells range in appearance from large immunoblastic or plasmablastic cells to cells with a more anaplastic morphology. PEL cells frequently express activation and terminally differentiated B-cell/plasma cell-related markers (eg, HLA-DR, CD30, CD38, IRF4, and CD138). Thence, ADC is a potential treatment of CD30-expressing classical Hodgkin and systemic anaplastic large cell lymphomas.

CD30 Targeted Therapy in Diffuse Large B-cell Lymphoma (DLBCL)

DLBCL is the most common type of NHL originating 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. Recent data suggests that CD30, a member of the tumor necrosis factor receptor family, is a potential therapeutic target in DLBCL. Thence, DLBCL is typically treated with chemoimmunotherapy such as antibody-drug conjugate therapy.

What Can We Do for You?

Hematological malignancy like lymphoma originates in lymph tissues and has a propensity to spread across other organs. Managing such tumors is challenging as conventional strategies like surgery and local treatment are not plausible options and there are high chances of relapse. Currently, immunotherapy especially the ADC has emerged as a new and promising therapeutic option, showing significant survival benefit for lymphoma in multiple disease sites and indications. BOC Sciences is a leading service provider in the field of developing breakthrough immunotherapy products for cancers therapy. Currently, we offer one-stop ADCs design and construction services targeting lymphoma. Our innovative linker technologies and effective bioconjugation platforms will facilitate your drug discovery and development.

References

  1. Bhatt, S. et al. CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma. Blood. 2013, 122: 1233-1242.
  2. Mikulska, M. et al. ESCMID study group for infections in compromised hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4). Clinical Microbiology and Infection. 2018, 2: 71-82.
  3. Graziani, G. et al. Antibody-drug conjugates: resurgent anticancer agents with multi-targeted therapeutic potential. Pharmacology & Therapeutics. 2022, 236: 108106.
  4. Patel, S.A. et al. The novel therapeutic landscape for relapsed/refractory diffuse large B cell lymphoma. Clinical Lymphoma Myeloma and Leukemia. 2021, 2152-2650.
* Only for research. Not suitable for any diagnostic or therapeutic use.

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