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Synonyms: BAT mAb | CT-011 | MDV9300
Compound class:
Antibody
Comment: Pidilizumab was developed with the intention of targeting the lymphocytic programmed death receptor-1 (PD-1) immune checkpoint. It is a humanized antibody derived from the murine BAT-1 monoclonal [6]. However, the originators (Medivation, licensed from CureTECH) have disclosed that the main mechanism of action of pidilizumab is not PD-1 blockade> The CureTECH website states that the primary molecular target is in fact the NOTCH ligand Delta-like 1 (DLL1). They go on to identify hypoglycosylated/nonglycosylated forms of PD-1, that are found on a distinct subpopulation of exhausted T cells, as secondary pidilizumab binding partners. Pidilizumab is an IgG1 isotype which suggests potent ADCC (antibody-dependent cell-mediated cytotoxicity) activity, which may or may not explain its clinical effect. This is in contrast to many of the other anti-PD-1 and anti PD-L1 mAbs which are IgG4 with much weaker effector activity, or that have been engineered to exhibit decreased FcR binding. This revelation around pidilizumab's MOA is discussed further in the 'In the Pipeline' blog post Medivation Decides That Their Drug Isn't What They Thought.
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record. |
| No information available. |
Summary of Clinical Use  |
| Pidilizumab is being assessed in clinical trial as a treatment for relapsed or refractory multiple myeloma (NCT02077959) and diffuse intrinsic pontine glioma and relapsed glioblastoma multiforme (NCT01952769). See also [2], [3] and [1]. |
| Mechanism Of Action and Pharmacodynamic Effects |
| Many cancer cells express PD-L1 [4,9-10], and this permits these malignant cells to 'evade' destruction by the immune system. Pidilizumab binds to the programmed cell death 1 (PD-1, PDCD1) receptor on activated T cells and prevents PD-L1 mediated immune checkpoint inhibition. This effects a normal T-cell response, leading to immune cell-mediated cancer cell destruction. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT01952769 | Anti PD1 Antibody in Diffuse Intrinsic Pontine Glioma | Phase 1/Phase 2 Interventional | Hadassah Medical Organization | ||
| NCT02077959 | Lenalidomide and Pidilizumab in Treating Patients With Relapsed or Refractory Multiple Myeloma | Phase 1/Phase 2 Interventional | Ohio State University Comprehensive Cancer Center | ||
