Tumor Microenvironment Modulation Service

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Modulating Tumor Microenvironment to Enhance TIL Therapy

The efficacy of TIL therapy is often hindered by the immunosuppressive tumor microenvironment (TME). This complex milieu involves various immune escape mechanisms, including those associated with tumor cells, immune cells, stromal cells, and factors like metabolism, genetics, and epigenetics. To overcome these challenges and enhance TIL therapy, recent research has focused on TME modulation strategies aimed at creating a favorable environment for TILs to function and eliminate cancer cells.

Fig.1 Tumor cell intrinsic and extrinsic mechanisms of resistance to immunotherapies. Fig.1 Intrinsic and extrinsic causes of immunotherapy resistance in tumor cells.¹

Tumor Microenvironment Modulation Service at Creative Biolabs

Creative Biolabs specializes in tumor microenvironment modulation services designed to enhance the efficacy of TIL therapy. Leveraging advanced bioinformatics analysis, we identify critical immunosuppressive factors and potential targets within the TME, such as various immune cells, cytokines, etc. Based on the analysis, our expert scientists meticulously design and optimize regulatory strategies to create a favorable environment for TILs to function effectively. Amongst, we implement rigorous in vitro and in vivo testing services to characterize these strategies to ensure their safety and efficacy, and we provide a wide selection of well-identified models and advanced technologies (i.e. imaging technologies) to empower the evaluation process.

Beyond strategy development, we also provide comprehensive support services to facilitate the clinical translation and commercialization of our customers' projects. Especially, we operate the whole process in strict adherence to GMP standards, ensuring complete traceability and regulatory compliance.

Fig.2 Process. (Creative Biolabs Original) Fig.2 Our service process.

Tumor Microenvironment Modulation Strategies

TME Components	Modulation Strategies	Description
Immune cells	Targeting immunosuppressive cells	This involves depleting or inhibiting immunosuppressive cells to create a more pro-inflammatory environment, allowing TILs to effectively eliminate cancer cells.
Immune cells	Engaging immune checkpoints	This includes the application of immune checkpoint inhibitors to disrupt inhibitory signals and boost TIL activation.
Extracellular matrix (ECM)	ECM remodeling	This strategy targets enzymes involved in ECM remodeling to improve TIL infiltration and migration within the tumor.
Extracellular matrix (ECM)	ECM degradation	This strategy involves the use of compounds to facilitate TIL access to tumor cells.
Cytokines and growth factors	Cytokine-secreting TILs	This involves the engineering of TILs to secrete specific cytokines that can enhance their anti-tumor activity and modulate the TME.
Cytokines and growth factors	Growth factor inhibition	This involves the blocking of growth factors to create a less supportive environment for tumor cells.
Blood vessels	Anti-angiogenic therapy	This involves the use of anti-angiogenic compounds to target blood vessels that reduce tumor blood supply and create a more hypoxic environment, which can enhance TIL activity.
Blood vessels	Vascular normalization	This involves normalizing tumor vasculature to improve TIL delivery and oxygenation within the tumor.

Modulative Targets in TME

We provide various targets to choose from for novel therapy design, which include but are not limited to:

Immune cells

Tregs, DCs, MDSCs, TAMs, NK cells

Extracellular matrix

MMPs, Integrins, Hyaluronan, Fibronectin, Collagen

Cytokines and growth factors

IL-2, IFN-γ, TNF-α, IL-10, TGF-β, IL-6, M-CSF, VEGF, PDGF

Blood vessels

VEGF, VEGFR, Endothelial Cells (ECs), HIF-1α, PDGF, PDGFR

Advantages

Advanced technologies support.
Complete research team implementation.
GMP-compliant laboratory equipment.
Selective targets providing.
Customized services.

As a pioneer in immunotherapy, Creative Biolabs is committed to developing TIL treatment by offering complete tumor microenvironment manipulation services. Our expert team leverages cutting-edge technologies to identify and target key immunosuppressive factors, optimize TIL function, and enhance therapeutic efficacy. By personalizing our strategies to specific demands, we strive to accelerate the development of innovative cancer treatments. Get in touch with us right now to discuss how our experience might help your research.

Reference

Czajka-Francuz, Paulina, et al. "Mechanisms of immune modulation in the tumor microenvironment and implications for targeted therapy." Frontiers in Oncology 13 (2023): 1200646. Distributed under Open Access license CC BY 4.0, without modification.

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