Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-target Effects with Reduced Off-tumor Toxicity for Use in Immuno-Oncology.

Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-target Effects with Reduced Off-tumor Toxicity for Use in Immuno-Oncology. Clin Cancer Res. 2019 Oct 10;: Authors: Autio KA, Boni V, Humphrey RW, Naing A Abstract The deep and durable antitumor effects of antibody-based immunotherapies such as immune checkpoint inhibitors (ICIs) have revolutionized oncology and transformed the therapeutic landscape for many cancers. Several anti-programmed death receptor 1 and anti-programmed death receptor ligand 1 antibodies have been approved for use in advanced solid tumors, including melanoma, non-small cell lung cancer (NSCLC), bladder cancer, and other cancers. ICIs are under development across many tumor types and preliminary results are compelling. However, ICIs have been associated with severe immune-related adverse events (irAEs), including rash, diarrhea, colitis, hypophysitis, hepatotoxicity, and hypothyroidism, which in some cases lead to high morbidity, are potentially life-threatening, and limit the duration of treatment. The incidence of severe irAEs increases further when programmed cell death-1 and programmed cell death ligand-1 inhibitors are combined with anti-CTLA-4 and/or other multi-drug regimens. Probody therapeutics, a new class of recombinant, proteolytically activated antibody prodrugs are in early development and are designed to exploit the hallmark of dysregulation of tumor protease activity to d...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research