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1159 A targeted masked ImmunoCytokine for CD138 expressing cancers
  1. Ryan Trinh1,
  2. Alex Vasuthasawat1,
  3. Sherie L Morrison2 and
  4. David Stover1
  1. 1Nammi Therapeutics Inc, Los Angeles, CA, USA
  2. 2University of California, Los Angeles, Los Angeles, CA, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Type I interferons (IFN) are well characterized pleiotropic cytokines with an array of anti-malignant cell activities. Although approved for use in various cancers, they’re most effective only at higher doses1 where side effects limit its effectiveness. QXL138AM is a masked immunocytokine comprised of an anti-CD138 antibody fused to a masked IFNα2a via a cleavable linker. Specific tumor targeting by the antibody combined with selective removal of the mask by proteases in the tumor environment were designed to maximize potency while minimizing systemic toxicities.

Methods Binding to CD138 was evaluated by ELISA plates coated with the extracellular domain (ECD) of CD138. The HEK-Blue IFNα/β reporter cell line was used to demonstrate IFN signaling in the presence or absence of a protease like matriptase. The inflammatory cytokine IP-10, which is known to be induced by IFNα2a, was monitored to gauge cytokine release in PBMCs caused by QXL138AM. A subcutaneous human xenograft tumor was used as a model in NSG mice to evaluate QXL138AM efficacy.

Results QXL138AM bound CD138 ECD. The HEK-Blue IFNα/β reporter assay showed the EC50 increased significantly between the non-targeted fusion control antibody QXL20AM and QXL138AM. The reporter assay also showed the EC50 increased compared to unmasked control QXL138A. In addition, the potency of QXL138AM IP-10 induction in PBMCs increased significantly when the mask was removed. Subcutaneous tumors in QXL138AM treated mice had an endpoint mean tumor area similar to QXL138A treated mice.

Conclusions QXL138AM bound CD138 ECD with nanomolar affinity while retaining its ability to dose dependently activate IFN signaling. Both antibody targeting to the cell as well as cleavage of the mask were found to enhance the potency of IFNA receptor activation. While unmasked QXL138A induced cytokines in PBMCs with a similar potency as WT IFNA, the mask on QXL138AM effectively inhibited the cytokine induction and matriptase cleavage restored full potency compared to IFNA or QXL138A. Finally, the peptide mask slightly altered its efficacy in a human xenograft tumor model compared to an analogous control lacking the mask. Together these data suggested that tumor targeting of IFNA, combined with selective mask removal in the tumor environment could maximize potency while minimizing IFNA receptor activation in normal tissues.


  1. Borden E, Ganes S, Gilles U, et al. Interferons at 50: past, current and future impact on biomedicine. Nat Rev. 2007;6:975–990

Ethics Approval This study was approved by The Institutional Animal Care and Use Committee which oversees animal programs, animal facilities, and policies ensuring appropriate care, ethical use and humane treatment of animals. Our IACUC protocol is 055303 within our IACUC approval ID: 22468–01. This study included animal subjects of mice, including immunocompromised mice shown in study alias number is 22468–03. Human cells and antibodies used in these studies are described and approved in our Biological Use Authorization (BUA-2019–288-001).

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