A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients.

BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent that selectively detects malignant tissue and can be used in real time to guide tumor resection. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of BLZ-100 and to explore the pharmacodynamics of fluorescence imaging of skin tumors. In this first-in-human study, BLZ-100 was administered intravenously to 21 adult patients 2 days before excising known or suspected skin cancers.

Phase 1 Safety, Pharmacokinetics, and Fluorescence Imaging Study of Tozuleristide (BLZ-100) in Adults With Newly Diagnosed or Recurrent Gliomas.

Background: Fluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate molecule for FGS of glioma and other tumor types.

Objective: To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma.

Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide.

Context.—: Resection of breast carcinoma with adequate margins reduces the risk of local recurrence and reoperation. Tozuleristide (BLZ-100) is an investigational peptide-fluorophore agent that may aid in intraoperative tumor detection and margin assessment.

Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors.

Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate.

Importance: Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is a chlorotoxin-based, tumor-targeting agent that has not yet been studied in HNSCC.

Objective: To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia.

Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors.

Image-Guided Tumor Resection.

Each year, millions of individuals undergo cancer surgery that is intended to be curative or at least a necessary component of a curative regimen. Particularly for those patients whose cancer harbors cells that are resistant to chemotherapy or radiation, the extent of surgery often defines whether they will be a survivor or casualty of the disease. For many solid tumor types, the difference in survival between patients who undergo gross total resection and those who have residual bulky disease is often profound.

Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve near-complete resection of brain tumors.

Object: The intraoperative clear delineation between brain tumor and normal tissue in real time is required to ensure near-complete resection without damaging the nearby eloquent brain. Tumor Paint BLZ-100, a tumor ligand chlorotoxin (CTX) conjugated to indocyanine green (ICG), has shown potential to be a targeted contrast agent. There are many infrared imaging systems in use, but they are not optimized to the low concentration and amount of ICG.

Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F.

The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease.

Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice.

T cell-derived cytokines are important in the development of an effective immune response, but when dysregulated they can promote disease. Here we identify a four-helix bundle cytokine we have called interleukin 31 (IL-31), which is preferentially produced by T helper type 2 cells. IL-31 signals through a receptor composed of IL-31 receptor A and oncostatin M receptor.

Cytokine-receptor pairing: accelerating discovery of cytokine function.

Over the past decade, advances in both gene discovery and ligand-receptor pairing techniques have led to the recognition that systematic pairing of 'orphan' database-derived cytokines and/or cytokine receptors with their cognate partners can lead to a marked acceleration in the elucidation of biological function. The sometimes-restricted tissue distribution of the receptor, coupled with the highly specific bioactivity of the corresponding ligand, can direct investigators rapidly towards regulatory function and site-of-action studies. The power of cytokine-receptor pairing to accelerate the understanding of function will be illustrated, citing several examples of candidate drug discoveries.

Interleukin-21 and the IL-21 receptor: novel effectors of NK and T cell responses.

Interleukin (IL)-21 was recently discovered using a functional cloning approach based on expression of its receptor. It is similar in domain organization and primary sequence to IL-2 and IL-15. Like these cytokines, IL-21 uses the common gamma chain of the IL-2/15 receptor, which forms a heterodimeric receptor complex with IL-21R.

Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions.

Cytokines that signal through Class II receptors form a distinct family that includes the interferons and interleukin 10 (IL-10). Recent identification of several IL-10 homologs has defined a cytokine subfamily that includes AK155, IL-19, IL-20, IL-22, and IL-24. Within this subfamily, IL-19, IL-20, and IL-24 exhibit substantial sharing of receptor complexes; all three are capable of signaling through IL-20RA/IL-20RB, and IL-20 and IL-24 both can also use IL-22R/IL-20RB.