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In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
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T-Cell Receptor Stimulation Enhances the Expansion and Function of CD19 Chimeric Antigen Receptor-Expressing T Cells
Natalia Lapteva1,2, Margaret Gilbert1, Iulia Diaconu1
1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, Texas.
Summary
Dual stimulation of CD19.CAR-T cells via native receptors and CARs can replace chemotherapy, leading to significant expansion and B-cell depletion in leukemia patients. This approach enhances CAR-T cell therapy efficacy.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Current CD19 chimeric antigen receptor-T cell (CD19.CAR-T) therapies necessitate preinfusion chemotherapy.
- The efficacy of CD19.CAR-T cells depends on adequate target antigen expression on B cells.
Purpose of the Study:
- To determine if stimulating CD19.CAR-T cells via their native receptors can substitute for cytoreductive chemotherapy.
- To assess the expansion and functional persistence of CD19.CAR-T cells without prior chemotherapy in B-cell acute lymphocytic leukemia patients.
Main Methods:
- Infusion of a low dose of CD19.CAR-modified virus-specific T cells (CD19.CAR-VST) without cytoreductive chemotherapy into 8 patients post-allogeneic stem cell transplant.
- Monitoring for viral reactivation and CD19.CAR-VST expansion, as well as B-cell depletion.
Main Results:
- No CD19.CAR-VST expansion was observed in the absence of viral reactivation.
- Significant expansion (up to 30,000-fold) of CD19.CAR-VSTs occurred in patients with viral reactivation, leading to CD19+ B-cell depletion.
- Five patients maintained remission for 42-60+ months.
Conclusions:
- Dual stimulation through T-cell receptors and CARs can enhance effector cell expansion and CAR-target cell killing.
- This dual stimulation approach can be effective even with low effector cell doses and without cytoreduction.
- This strategy offers a potential alternative to chemotherapy in CD19.CAR-T cell therapy.
