Precision Immune Engineering

Dr. Xiaojing Chen

The focus of our research group is the development, mechanistic characterization, and translational implementation of innovative immunotherapeutic strategies to overcome resistance in difficult-to-treat solid and hematological malignancies. By bridging synthetic biology, molecular oncology, and cellular immunology, we aim to engineer next-generation cell therapies and targeted biological agents that redirect cellular signaling networks toward potent anti-tumor responses.

Schematic overview of our translational platform for engineering and characterizing high-specificity T-cell receptors (TCRs) to overcome tumor immune tolerance. © made in Biorender and powerpoint

TCR-Based Cell Therapies & T-Cell Engineering

While therapies such as CD19 chimeric antigen receptor T cells (CD19 CAR-T) have demonstrated remarkable success in hematologic malignancies, achieving durable responses in solid tumors remains the greatest challenge in immunotherapy. TCR-based T-cell approaches hold immense promise for treating solid tumors due to the high sensitivity and target specificity of the T-cell receptor. A primary pillar of our research focuses on developing advanced T-cell receptor (TCR)-based cell therapies. We systematically search for and validate high-value intracellular cancer targets presented on MHC complexes, spanning shared oncogenic driver neoantigens, cancer-germline/testis antigens, and viral oncoproteins. To maximize therapeutic efficacy, we develop and benchmark engineered TCR-T cells alongside soluble T-cell engagers. Our group utilizes high-throughput functional screening, live-cell imaging, 3D organoid models, and humanized mouse models to optimize T-cell persistence, counteract microenvironmental immunosuppression, and prevent T-cell exhaustion in solid tumors.

Biotherapeutic Oncogenic Signal Targeting & Novel Immune Modulators

Expanding beyond conventional target paradigms, our group develops modular biotherapeutics for cancer treatment. We aim to explore signaling pathways that can direct both cell cytotoxicity and immunogenicity to provide a versatile, off-the-shelf platform for next-generation cancer therapy.

Translational Integration within the DKTK

Operating at the intersection of fundamental biological discovery and preclinical development, our group leverages functional screening, proteomics, and single-cell multi-omics infrastructures. Within the DKTK framework, we actively collaborate with clinical partners and core facilities to accelerate the bench-to-bedside translation of novel cellular and biological immunotherapies.

Future Projects & Goals

Our mission is to establish next-generation engineered translational immunotherapies by combining advanced adoptive cell therapies with novel biological signal-modulation strategies:

TCR-Based T-Cell Engineering: We are expanding our TCR-T cell platform to target driver neoantigens and cancer-germline antigens. Key projects focus on engineering synthetic co-stimulatory switches and metabolic circuits that sustain T-cell effector functions and overcome exhaustion in solid tumors.
Novel Immunomodulators: We are developing immunomodulators and engineered biotherapeutics to direct cellular signaling towards immunogenic outputs.
Translational Integration: Utilizing organoid platforms and single-cell multi-omics, our objective within the DKTK is to benchmark cellular versus soluble biotherapeutic formats for rapid clinical translation.