Related Experiment Video
Updated: May 4, 2026
Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments
Published on: April 30, 2021
Enhancing Patient Lymphocyte Response to Peritoneal Malignancies Using a Personalized Immunocompetent Microfluidic
Abstract:
Harnessing patient immune cells via adoptive cellular therapy is a promising cancer therapeutic strategy. However, major challenges remain for advanced solid malignancies, including difficulty isolating sufficient tumor infiltrating lymphocytes (TILs) and limited targeting of diverse neoantigens in heterogenous tumors. To address this, we have developed a tumor-on-a-chip platform with co-cultured patient-derived tumor cells, autologous peripheral blood mononuclear cells (PBMCs), and lymphoid tissue-derived antigen presenting cells. This approach generates organoid interacting lymphocytes (OILs) with enhanced anti-tumor activity. In peritoneal malignancies, OIL-induced cytotoxicity of patient-matched tumor cells surpasses both TILs and static-expanded PBMCs. We find that this improved performance was linked to increased CD8 + T and NK cells among OILs, and increased effector cytokine polyfunctionality, particularly Granzyme A. Our platform represents a versatile and scalable approach to generate patient-specific therapeutic lymphocytes even when TILs are insufficient, offering a promising avenue to treat diverse solid tumors associated with poor outcomes under current immunotherapies.
Teaser:
A tumor-on-a-chip device primes patient immune cells with tumor recognition for personalized immunotherapy applications.
Insights
A novel tumor-on-a-chip platform generates organoid interacting lymphocytes (OILs) for enhanced cancer immunotherapy. This approach overcomes challenges with tumor infiltrating lymphocytes (TILs), offering improved anti-tumor activity for solid malignancies.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Adoptive cellular therapy shows promise for cancer treatment but faces challenges in solid tumors.
- Difficulty in isolating sufficient tumor-infiltrating lymphocytes (TILs) and targeting diverse tumor neoantigens limits efficacy.
- Current immunotherapies have limited success in advanced solid malignancies.
Purpose of the Study:
- To develop a novel platform for generating potent patient-specific therapeutic lymphocytes.
- To overcome limitations of traditional adoptive cellular therapy for solid tumors.
- To enhance anti-tumor activity by priming immune cells with tumor recognition.
Main Methods:
- Developed a tumor-on-a-chip platform co-culturing patient tumor cells, peripheral blood mononuclear cells (PBMCs), and antigen-presenting cells.
- Generated organoid interacting lymphocytes (OILs) from co-cultured cells.
- Assessed OIL anti-tumor activity and cellular composition in peritoneal malignancies.
Main Results:
- OILs demonstrated superior cytotoxicity against patient-matched tumor cells compared to TILs and PBMCs.
- OILs showed an increase in CD8+ T and NK cells and enhanced effector cytokine polyfunctionality (Granzyme A).
- The platform successfully generated patient-specific lymphocytes, even with insufficient TILs.
Conclusions:
- The tumor-on-a-chip platform provides a scalable method to generate effective therapeutic lymphocytes for solid tumors.
- This approach enhances anti-tumor activity by increasing cytotoxic immune cell populations and function.
- Represents a promising strategy for personalized immunotherapy in difficult-to-treat cancers.
