Development of TSHR-CAR NK-92 cells for Differentiated Thyroid Cancer

Area of Science:

• Immunotherapy
• Oncology
• Cellular Therapy

Background:

• Differentiated thyroid cancer (DTC) presents limited treatment options for relapsed, metastatic, or refractory cases.
• Chimeric antigen receptor (CAR)-modified Natural Killer (NK) cells are emerging as effective treatments for resistant cancers.
• Thyroid-stimulating hormone receptor (TSHR) is expressed in DTC, offering a specific target for therapy.

Purpose of the Study:

• To develop an innovative immunotherapy for DTC using TSHR-targeted CAR-modified NK-92 cells.
• To evaluate the efficacy and safety of these engineered NK cells against DTC.

Main Methods:

• Development of NK-92 cells engineered with a CAR targeting TSHR.
• Assessment of modified NK cell cytotoxicity, degranulation, and cytokine release against DTC cell lines.
• Evaluation of the anti-tumor efficacy of irradiation-treated CAR-NK cells in a mouse model of DTC.

Main Results:

• TSHR-CAR-modified NK-92 cells demonstrated enhanced killing of TSHR-positive DTC cells.
• Modified cells exhibited increased degranulation and cytokine production.
• Irradiation-treated CAR-NK cells halted proliferation while retaining potent anti-tumor activity, leading to significant tumor suppression in mice.

Conclusions:

• TSHR-CAR-modified NK-92 cells represent a potent therapeutic strategy for differentiated thyroid cancer.
• This approach offers a promising, off-the-shelf, targeted immunotherapy option for DTC.
• Further development of CAR-NK cell therapy holds potential for advancing DTC treatment.