Related Experiment Video
Updated: Dec 23, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with
Kenneth R Gundle1,2, Gary B Deutsch3, Howard J Goodman3
1Department of Orthopaedics & Rehabilitation, Oregon Health & Science University, Portland, Oregon.
Purpose:
A persistent issue in cancer drug development is the discordance between robust antitumor drug activity observed in laboratory models and the limited benefit frequently observed when patients are treated with the same agents in clinical trials. Difficulties in accurately modeling the complexities of human tumors may underlie this problem. To address this issue, we developed Comparative In Vivo Oncology (CIVO), which enables in situ investigation of multiple microdosed drugs simultaneously in a patient's tumor. This study was designed to test CIVO's safety and feasibility in patients with soft tissue sarcoma (STS).
Patients And Methods:
We conducted a single arm, prospective, 13-patient pilot study. Patients scheduled for incisional biopsy or tumor resection were CIVO-injected 1 to 3 days prior to surgery. Saline or microdoses of anticancer agents were percutaneously injected into the tumor in a columnar fashion through each of eight needles. Following excision, drug responses were evaluated in the injected tissue.
Results:
The primary objective was met, establishing CIVO's feasibility and safety. Device-related adverse events were limited to transient grade 1 nonserious events. In addition, biomarker evaluation of localized tumor response to CIVO microinjected drugs by IHC or with NanoString GeoMx Digital Spatial Profiler demonstrated consistency with known mechanisms of action of each drug, impact on the tumor microenvironment, and historic clinical activity.
Conclusions:
These results are an advance toward use of CIVO as a translational research tool for early evaluation of investigational agents and drug combinations in a novel approach to phase 0 trials.See related commentary by Sleijfer and Lolkema, p. 3897.
Insights
The Comparative In Vivo Oncology (CIVO) system was found safe and feasible for testing multiple cancer drugs simultaneously in soft tissue sarcoma patients. This tool aids in evaluating new cancer therapies early in clinical trials.
Area of Science:
- Oncology
- Translational Research
- Drug Development
Background:
- Cancer drug development faces challenges due to discrepancies between preclinical models and clinical trial outcomes.
- Accurate modeling of human tumor complexity is crucial for effective drug development.
- The Comparative In Vivo Oncology (CIVO) system was developed to address these limitations.
Purpose of the Study:
- To evaluate the safety and feasibility of the CIVO system in patients with soft tissue sarcoma (STS).
- To investigate the potential of CIVO as a translational research tool for early drug evaluation.
Main Methods:
- A prospective, single-arm pilot study involving 13 STS patients.
- CIVO system was used to microinject anticancer agents or saline into tumors 1-3 days before surgical resection.
- Drug responses and biomarker changes in injected tumor tissue were analyzed post-excision.
Main Results:
- The CIVO system demonstrated feasibility and safety, with only transient, nonserious adverse events.
- Biomarker analysis confirmed drug-specific effects, including impact on the tumor microenvironment.
- Observed responses were consistent with known drug mechanisms and historical clinical activity.
Conclusions:
- CIVO is a safe and feasible tool for in situ evaluation of multiple microdosed drugs in patient tumors.
- The system shows promise as a translational research platform for early-phase (Phase 0) clinical trials.
- CIVO facilitates the investigation of investigational agents and drug combinations in a patient-specific context.
More Related Videos
06:05Author Spotlight: Multiplex Immunofluorescence Combined with Spatial Image Analysis for the Clinical and Biological Assessment of the Tumor Microenvironment
Published on: June 2, 2023
05:32Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice
Published on: January 7, 2019