Localized Chemotherapy Based on Injectable Hydrogel Boosts the Antitumor Activity of Adoptively Transferred T...

Area of Science:

• Immunology
• Biomedical Engineering
• Oncology

Background:

• Adoptive T cell therapy shows promise for hematological malignancies but faces challenges in solid tumors due to the immunosuppressive tumor microenvironment.
• The immunosuppressive tumor microenvironment hinders the efficacy of adoptive T cell therapy in solid tumor treatment.

Purpose of the Study:

• To develop a thermoresponsive hydrogel loaded with doxorubicin (DOX@Gel) as a preprocessing strategy to reprogram the immunosuppressive tumor microenvironment.
• To evaluate the combined efficacy of DOX@Gel and adoptive T cell therapy against solid tumors.

Main Methods:

• Utilized a thermoresponsive hydrogel loaded with doxorubicin (DOX@Gel) for local chemotherapy.
• Administered DOX@Gel as a preprocessing strategy before adoptive T cell transfer.
• Assessed anti-tumor efficacy, T cell proliferation and effector function, and changes in immunosuppressive cell populations (myeloid-derived suppressor cells and Tregs).

Main Results:

• The combination therapy of DOX@Gel and adoptive T cell transfer demonstrated enhanced anti-tumor efficacy compared to monotherapies.
• DOX@Gel treatment led to the release of tumor-associated antigens, boosting T cell responses.
• DOX@Gel significantly reduced myeloid-derived suppressor cells and Tregs within the tumor microenvironment.

Conclusions:

• DOX@Gel effectively reprograms the immunosuppressive tumor microenvironment, overcoming a key limitation of adoptive T cell therapy for solid tumors.
• This combination strategy holds potential for improving the clinical application of adoptive T cell therapy in solid tumor treatment.