Tumor-microenvironment-modulating microspheres to augment tumor-infiltrating lymphocyte therapy against solid tumors

Area of Science:

• Oncology
• Immunotherapy
• Biomaterials Science

Background:

• Tumor-infiltrating lymphocyte (TIL) therapy shows promise for solid tumors but faces challenges.
• Limited TIL numbers and activity are caused by the dense extracellular matrix (ECM) and immunosuppressive tumor microenvironment (TME).
• Current TIL preparation is time-consuming and yields suboptimal treatment efficacy.

Purpose of the Study:

• To develop an effective strategy for enhancing TIL therapy by modulating the TME prior to TIL collection.
• To improve the quantity, quality, and anti-cancer activity of TILs for improved therapeutic outcomes.

Main Methods:

• Alginate-based hydrogel microspheres were co-loaded with hyaluronidase (HAase) and chemokine CXCL9.
• Intratumoral injection of these microspheres was used to degrade ECM and recruit lymphocytes.
• TILs were collected from pre-treated tumors for ex vivo expansion and re-infusion.

Main Results:

• Microsphere injection effectively modulated the TME, significantly increasing TIL numbers within tumors.
• Collected TILs demonstrated accelerated ex vivo expansion, enhanced activity, and improved anti-exhaustion capabilities.
• Re-infused TILs effectively inhibited tumor growth and metastasis in preclinical models.

Conclusions:

• Modulating the TME before TIL collection is a viable and clinically practical approach to enhance TIL therapy.
• This strategy offers a promising method to overcome limitations of current TIL treatments and improve patient outcomes.
• The developed hydrogel microsphere system represents a significant advancement in cancer immunotherapy.