CIVO™ Platform –
An Elegant Approach to Cancer Drug Development
Assessment of anti-cancer drug efficacy is an imprecise and challenging undertaking. Decisions on which patient population to treat with what drug combination are often based on data from animal models and later, on data from lengthy human trials that expose patients to often-toxic levels of a drug prior to obtaining tumor response. In both of these testing models, only one drug regimen can be tested at a time and drug response is compared between different individuals, a known source of major variability.
To address these challenges and improve our ability to predict patient response to drugs in development, Presage has developed an arrayed microinjection and analysis platform called CIVO™.
The CIVO™ platform consists of a device that allows for simultaneous delivery of test drugs into defined positions within a living tumor, coupled with automated, quantitative image-based analysis of specific tumor responses. The arrayed microinjection procedure is performed using a hand-held device in live patients.
Each needle of the arrayed microinjection device is positioned to deliver sample into one of up to eight distinct locations within a tumor. The microinjection device deposits a uniform, column-like core of drug through the tumor, allowing sampling of multiple tissue depths to assess consistency of tumor response to drug exposure. Given the tumor heterogeneity observed in the oncology clinic, the drug column provides the potential to investigate how different tumor environments such as oxygen levels or presence of vasculature impact drug efficacy. The amounts of drug delivered per injection site are usually less than 1/100th of what would be delivered to a patient’s body for therapeutic purposes. Studies on thousands of mice, and in both canine and human patients with lymphoma, have demonstrated that, as expected, these drug “microdoses” do not result in significant toxic side effects.
Later, typically 24 hours after injection, the tumor is resected for analysis to assess responses to the drugs. Multiple molecular responses are tracked for each drug injection by sampling thin sections along the injection column. These include specific molecular markers for drug mechanism-related effects, drug target or cancer pathway engagement by the drug and ultimately, tumor cell death responses.
High resolution scanning of the entire microscopy slide is used to capture images of every cell from each tissue section generated. These digitized images are then processed with CIVO™ Analyzer, a custom image analysis platform. CIVO™ Analyzer couples automated detection of the drug injection sites, characterization and analysis of cellular and tissue architecture, molecular marker-specific algorithms and cross-section registration to quantify multiple measures of drug response from various tumor depths along each injection column. Such analysis creates a comprehensive portrait of drug response by looking at elements such as how the drug induces death of cancer and stromal cells, how the drug provokes a response by the immune system and how drugs work together to enhance effects.
Presage is evaluating its CIVO™ platform in a first-in-human study in collaboration with the Seattle Cancer Care Alliance (SCCA) and the Fred Hutchinson Cancer Research Center, with funding support from the National Cancer Institute (NCI). CIVO™ also is being employed in preclinical models including canine cancer patients and xenograft human tumors in mice.
CIVO™ technology can drive decision-making in cancer drug portfolios, enabling comparison and validation of cancer therapies and combinations in biologically relevant tumors earlier in the drug development process than is currently possible with conventional approaches.