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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Preclinical Evaluation of Novel Folate Receptor 1-Directed CAR T Cells for Ovarian Cancer
Julie Daigre1, Manuel Martinez-Osuna1, Maria Bethke1
1Miltenyi Biotec B.V. & Co. KG, Friedrich-Ebert-Strasse 68, 51429 Bergisch Gladbach, Germany.
Abstract:
Treatment options for ovarian cancer patients are limited, and a high unmet clinical need remains for targeted and long-lasting, efficient drugs. Genetically modified T cells expressing chimeric antigen receptors (CAR), are promising new drugs that can be directed towards a defined target and have shown efficient, as well as persisting, anti-tumor responses in many patients. We sought to develop novel CAR T cells targeting ovarian cancer and to assess these candidates preclinically. First, we identified potential CAR targets on ovarian cancer samples. We confirmed high and consistent expressions of the tumor-associated antigen FOLR1 on primary ovarian cancer samples. Subsequently, we designed a series of CAR T cell candidates against the identified target and demonstrated their functionality against ovarian cancer cell lines in vitro and in an in vivo xenograft model. Finally, we performed additional in vitro assays recapitulating immune suppressive mechanisms present in solid tumors and developed a process for the automated manufacturing of our CAR T cell candidate. These findings demonstrate the feasibility of anti-FOLR1 CAR T cells for ovarian cancer and potentially other FOLR1-expressing tumors.
Insights
New chimeric antigen receptor (CAR) T cells targeting the FOLR1 antigen show promise for treating ovarian cancer. These engineered T cells demonstrated efficacy in preclinical models, offering a potential new therapy for this disease.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Ovarian cancer treatment options are limited, with a significant need for effective, targeted therapies.
- Chimeric antigen receptor (CAR) T cells offer a promising approach for targeted cancer treatment due to their persistent anti-tumor activity.
Purpose of the Study:
- To develop and preclinically assess novel CAR T cells targeting ovarian cancer.
- To identify and validate suitable targets for CAR T cell therapy in ovarian cancer.
Main Methods:
- Identified potential CAR targets on ovarian cancer samples, confirming high expression of FOLR1.
- Designed and tested anti-FOLR1 CAR T cell candidates in vitro against ovarian cancer cell lines and in vivo using a xenograft model.
- Assessed CAR T cell functionality in immune-suppressive conditions and developed an automated manufacturing process.
Main Results:
- Confirmed high and consistent expression of the tumor-associated antigen FOLR1 in primary ovarian cancer samples.
- Demonstrated the efficacy of anti-FOLR1 CAR T cells against ovarian cancer cell lines and in a preclinical xenograft model.
- Validated CAR T cell function in assays mimicking the tumor microenvironment and established an automated manufacturing process.
Conclusions:
- Anti-FOLR1 CAR T cells are a feasible therapeutic strategy for ovarian cancer.
- This approach holds potential for treating other tumors that express FOLR1.
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