Predicting responses to chemotherapy in the context that matters - the patient

Abstract

Guided by the belief that the most important setting for understanding tumor response to drugs is the human patient, we developed a technology called CIVO. CIVO enables analysis of up to 8 therapies simultaneously in a patient's tumor, without inducing systemic toxicity and while maintaining the integrity of the native tumor microenvironment.

Keywords: Cancer; clinical drug development; human lymphoma; in vivo; microinjection; preclinical; tumor microenvironment; tumor response.

Figures

Figure 1.

The CIVO tumor microinjection platform – localized responses predict systemic effects of chemotherapy. (A-B) The CIVO platform consists of a handheld array of up to 8 needles capable of simultaneously penetrating subcutaneous solid tumors and delivering easily identifiable column-like tracks of drug spanning the z axis of the tumor. (C) A chemically inert fluorescent tracking marker is co-injected through each needle to indicate each injection site within the tumor. (D) Tumor responses are assessed following tumor resection via histologic staining of tumor cross-sections sampled perpendicular to each injection column. These are quantified by an automated image-based analysis package that outlines radial zones where cells are super-exposed to drug ( 400 μm - yellow ring). (E-F) The fraction of biomarker-positive cells (cleaved caspase-3 [CC3]) is plotted as a function of radial distance from the injection site and localized tumor responses are compared to tumor growth inhibition after systemic treatment.