InvivoGen provides a family of anti-hCD70-derived monoclonal antibodies (mAbs) in multiple human isotypes.
They feature:
- the variable region of vorsetuzumab targeting the human (h)CD70 and
- a constant region that mediates different effector functions depending on the isotype.
The effector functions of the human isotypes in this family include antibody‑dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). You may choose between:
— IgG1 for high effector functions
(Anti-hCD70-hIgG1 is the biosimilar of the clinical antibody vorsetuzumab ),
— IgG1fut for even higher effector functions
(engineered non-fucosylated (fut) constant region), or
— IgG1NQ for no effector functions
(engineered N-glycosylation mutated constant region).
InvivoGen's mAbs have been generated by recombinant DNA technology, produced in Chinese hamster ovary (CHO) cells, and purified by affinity chromatography.
Key features of the Anti-hCD70 isotype family
- Clinically-relevant variable region targeting human CD70 (vorsetuzumab)
- Choice of different constant regions for high/low effector functions
- Functionally validated by flow cytometry and ADCC assay
- The absence of bacterial contamination has been confirmed
Vorsetuzumab is a humanized IgG1 mAb targeting the immune checkpoint (IC) molecule CD70 (aka CD27 ligand or CD27L). This mAb can kill tumor cells through antibody-dependent cell-mediated responses (ADCC & ADCP). In addition, vorsetuzumab can also be conjugated with small molecular antitumor drugs to form a new type of targeted therapeutic molecule called antibody-drug conjugates (ADCs) with accurate targeting and greater lethality [1]. Currently, a non-fucosylated version of this mAb (SEA-CD70) is undergoing clinical evaluation in a phase I study in patients with myeloid malignancies (NCT04227847) [2]. In the appropriate context of T cell receptor engagement, the interaction of CD27 with its ligand CD70 (also known as CD27L) promotes T cell activation, maturation of effector capacity, and T cell memory [3-4].
References:
1. Ryan MC, et al., 2010. Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody-drug conjugate SGN-75. Br J Cancer. 24;103(5):676-84.
2. Flieswasser, T., Van den Eynde, A., Van Audenaerde, J. et al., 2022. The CD70-CD27 axis in oncology: the new kids on the block. J Exp Clin Cancer Res 41, 12.
3. Vitale LA, et al.,2012. Development of a human monoclonal antibody for potential therapy of CD27-expressing lymphoma and leukemia. Clin Cancer Res.;18(14):3812-21.
4. Sanborn RE, et al., 2022. Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors. J Immunother Cancer. 10(8):e005147.
