November 16, 2022

A Microfluidic Device for High Throughput Screening of Tumor-reactive T Cells for Clinical Applications in Personalized Cancer Immunotherapy

1st Call, iDoc

Short Summary

The goal of this project is to probe specific reactivity of T cells originating from a sample (tumor infiltrating T cells) are placed in contact with one of the APC out the patient specific cell library transduced to express relevant neo-antigens. Early signs of T-cell activation will be optically measured by tracking the increase of intracellular Ca2+ concentration following the T cell receptor (TCR) interaction. For this purpose, we develop a droplet microfluidics platform that will combine high speed and high yield cell pairing in single droplet optimize the cell-cell contact by appropriate in-droplet flow recirculation and fast sorting based on calcium imaging.

Goals

This project aims at assessing single T cell reactivity by a combinatorial approach where all T cell from a sample (tumor infiltrating T cells) are placed in contact with one of the APC out the patient specific cell library transduced to express relevant neo-antigens. Early signs of T-cell activation will be optically measured by tracking the rapid increase of intracellular Ca2+ concentration following the T cell receptor (TCR). For this purpose, we will develop a droplet microfluidics platform that will combine high speed and high yield cell pairing in single droplet, optimize the cell-cell contact by appropriate in-droplet flow recirculation and fast sorting based on calcium imaging.

Significance

As we aim at clinical applications, we focus on the full system functionality with cell numbers that are relevant for the clinical use. We will optimize our system and the functional protocols to prove efficient use with small samples. We plan, at the end of the project, to transfer our droplet microfluidic platform in clinical setting. Tumor biopsies and peripheral blood from patients with lung or colorectal cancer will be obtained from the Biobank of the DO. Relevant potential neo-antigens and other tumor antigens will be determined using our comprehensive multi-omics algorithm, while TILs will be derived and expanded. The tumor-reactive cells isolated using the droplet microfluidic platform will be isolated and expanded using the established standard operating procedures from the cell manufacturing facility (CMF-GMP) in order to validate the generation of clinical-grade tumor-specific T cells for personalized immunotherapy (ACT).

Background

Immunotherapy holds great promise and potential for cancer treatment and many trials are under way. Unfortunately, even if successful, routine clinical use remains impossible today. Identification of suitable tumor antigens is very time consuming and resource intense which limits the use of cell-based Immunotherapy in clinical practice. The scope of this project is to develop high-throughput methods for fast identification of suitable target antigens and “production” of tumor-destroying immune cells.

Publications

Arnaud, M. Duchamp, S. Bobisse, P. Renaud, G. Coukos, A. Harari, Biotechnologies to tackle the challenge of neoantigen identification, Current Opinion in Biotechnology,65, 2020, pp 52-59, doi.org/10.1016/j.copbio.2019.12.014

Patents / Startups

Microfluidic device for sample encapsulation and method for operation thereof (EP21208067), EPFL license acquired by the startup Parithera in 2022

iDoc

Prof. Dr. Philippe Renaud

Microsystems Laboratory 4, EPFL

Co-Investigators

Dr. Alex Harari, Dpt. Of Oncology, CHUV and Ludwig Institute for Cancer Research, Lausanne
Prof. George Coukos, Dpt. Of Oncology, CHUV and Ludwig Institute for Cancer Research, Lausanne