First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors

• Published in: Clinical cancer research Vol. 25; no. 1; pp. 99 - 109
• Main Authors: Strauss, Julius, Heery, Christopher R., Kim, Joseph W., Jochems, Caroline, Donahue, Renee N., Montgomery, Agnes S., McMahon, Sheri, Lamping, Elizabeth, Marté, Jennifer L., Madan, Ravi A., Bilusic, Marijo, Silver, Matthew R., Bertotti, Elisa, Schlom, Jeffrey, Gulley, James L.
• Format: Journal Article
• Language: English
• Published: United States 01.01.2019
• Subjects: Adult; Aged; Cell Line, Tumor; DNA Fragmentation - drug effects; Drug-Related Side Effects and Adverse Reactions - immunology; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Humans; Immunoglobulin G - administration & dosage; Immunoglobulin G - adverse effects; Influenza, Human - chemically induced; Influenza, Human - pathology; Interleukin-12 - administration & dosage; Interleukin-12 - adverse effects; Interleukin-12 - immunology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Male; Maximum Tolerated Dose; Middle Aged; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; Neoplasms, Second Primary - drug therapy; Neoplasms, Second Primary - immunology; Neoplasms, Second Primary - pathology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - adverse effects; Transaminases - metabolism

The NHS-IL12 immunocytokine is composed of two IL12 heterodimers fused to the NHS76 antibody. Preclinical studies have shown that this antibody targets IL12 to regions of tumor necrosis by binding histones on free DNA fragments in these areas, resulting in enhanced antitumor activity. The objectives...