Enhancing Patient Lymphocyte Response to Peritoneal Malignancies Using a Personalized Immunocompetent Microfluidic...

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.