The Immuno-Oncology Hollow Fiber Assay

• In order to facilitate the translation of novel immunotherapies from bench to bedside, continued development of predictive preclinical models is essential. Herein, we developed the immuno-oncology hollow fiber assay (HFA) to bridge the gap between cell based in vitro assays and more complex mouse models for evaluation of immuno-oncological agents. The colorectal cancer (CRC) cell line HCT116-GFP and human peripheral blood mononuclear cells (PBMCs) were co-cultured inside semipermeable hollow fibers. As a proof of concept, aCD3 and IL-2 was used to induce immune cell-mediated cancer cell death. During in vitro characterization of the model system, an enhanced effect of aCD3 and IL-2 was observed in the HFA compared to conventional monolayers. Further investigation demonstrated that increased cell proximity alone is sufficient to augment immune cell activation and effector function. To assess the functionality of the assay in vivo, a pilot study was performed using nude mice. Hollow fibers were surgically implanted intraperitoneally (i.p.) and the mice received local injections of aCD3 at the time of implantation and/ or systemic IL-2 via i.p. injection once daily for 3 consecutive days. Compared to untreated mice and mice receiving IL-2 alone, the combination of aCD3 and IL-2 resulted in a significant decrease in cancer cell viability. Traditional in vivo models often necessitate lengthy observation periods to monitor tumor growth and treatment response. We have developed a simplified model system that enables initial in vivo evaluation of immunological agents on cancer and immune cells of human origin within a matter of days. 

Ämnesord

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Immuno-oncology

preclinical modeling

mouse models

hollow fibers

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)