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Updated: Sep 10, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
B7-H3 and CSPG4-targeted CAR T cells as potent effectors in anaplastic thyroid cancer
Giulia Cattaneo1,2, Marco Ventin1,2, Shahrzad Arya1,2
1Division of Gastrointestinal and Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Background:
Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy with poor survival and no available effective therapy. This unmet clinical need led us to investigate chimeric antigen receptor (CAR) T cells s as potential treatment option for this malignant disease. As target tumor antigens of our CAR T cell therapy, we selected the chondroitin sulfate proteoglycan 4 (CSPG4) and the B7-homolog 3 (B7-H3), as they are both highly and homogeneously expressed on different types of thyroid carcinoma cell lines and tissues, including ATC. Importantly, both CSPG4 and B7-H3 have a low distribution on normal tissues, thus limiting 'on-target off-tumor' CAR T-related toxicities.
Methods:
We generated CSPG4-specific and B7-H3-specific CAR T cells by utilizing a second-generation CAR construct comprised of a CD28 costimulatory domain and tested their antitumor activity in vitro and in an orthotopic xenograft murine model of ATC.
Results:
We demonstrated that thyroid cancer cells are specifically recognized and effectively eradicated in vitro by CSPG4-targeted and B7-H3-targeted CAR T cells. Additionally, both CAR T cell types were able to mediate significant control or complete eradication of primary ATC tumors when mice were treated with CSPG4 CAR T cells or B7-H3 CAR T cells, respectively.
Conclusion:
Overall, in this study we identified CSPG4 and B7-H3 as valuable target antigens in thyroid cancer and demonstrated that CAR T cell immunotherapy can be a valuable therapeutic option for ATC patients. Our findings provide the translational basis for exploring CAR T cell immunotherapies targeting CSPG4 and B7-H3 with ATC patients who do not respond or relapse after first line treatment.
Insights
Chimeric antigen receptor (CAR) T cell therapy targeting CSPG4 and B7-H3 shows promise for anaplastic thyroid cancer (ATC). This immunotherapy effectively eradicated ATC cells in vitro and in preclinical models, offering a potential new treatment for this aggressive cancer.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited therapeutic options and poor prognosis.
- Chimeric antigen receptor (CAR) T cell therapy presents a potential treatment avenue for ATC.
- CSPG4 and B7-H3 are highly expressed on ATC and minimally on normal tissues, making them suitable targets to minimize toxicity.
Purpose of the Study:
- To investigate the efficacy of CAR T cells targeting CSPG4 and B7-H3 in anaplastic thyroid cancer.
- To evaluate the potential of CSPG4 and B7-H3 as therapeutic targets for ATC immunotherapy.
Main Methods:
- Generated CSPG4-specific and B7-H3-specific CAR T cells using a second-generation construct with a CD28 costimulatory domain.
- Assessed the antitumor activity of these CAR T cells in vitro against thyroid cancer cell lines.
- Evaluated the in vivo efficacy in an orthotopic xenograft murine model of ATC.
Main Results:
- Thyroid cancer cells were specifically recognized and effectively eradicated in vitro by both CSPG4-targeted and B7-H3-targeted CAR T cells.
- Treatment with CSPG4 CAR T cells or B7-H3 CAR T cells resulted in significant tumor control or complete eradication in a preclinical ATC model.
- Both CAR T cell types demonstrated potent antitumor activity against ATC in vivo.
Conclusions:
- CSPG4 and B7-H3 are validated as valuable target antigens for thyroid cancer immunotherapy.
- CAR T cell immunotherapy targeting CSPG4 and B7-H3 offers a promising therapeutic strategy for anaplastic thyroid cancer.
- These findings support the clinical exploration of CSPG4 and B7-H3 CAR T cell therapies for ATC patients with refractory or relapsed disease.
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