Label-free Critical Quality Attributes of CAR T-Cell Products

This NIIMBL project will utilize novel biophysical and optical characterization methods to identify at least two CQAs for human T cells and engineered CAR-T cell products that will be correlated with known preclinical positive characteristics.
Categories
Cell and Gene therapies
Equipment and Supplies
Data

Industry Need

  • Cell therapy products comprising engineered T cells (e.g., CAR-T cells) require manufacturing innovation to identify and select for critical quality attributes (CQAs) defining safety and efficacy. 
  • CQAs that will enable analysis and “sorting” of qualified donor cells and/or the engineered cells – ideally without use of cell-labeling and amenable to analysis of low cell numbers and fluid volumes – can significantly improve product safety, efficacy, and production costs. 
  • While approaches using small-volume microfluidics, optic, and mechanics have been demonstrated for other cell types including human stem cells, this will be an innovative manufacturing technology approach for CAR-T cells. 

Approach

MIT, Bristol Myers Squibb, and LumaCyte utilized novel biophysical and optical characterization methods to identify at least two CQAs for human T cells and engineered CAR-T cell products that will be correlated with known preclinical positive characteristics.  


This project lays the groundwork for data analysis and future experiments that correlate CQAs with positive therapeutic outcome in human clinical trials and marketed products, providing the first validated set of CAR T cell CQAs amenable to efficient production. 

Impacts

To the team’s knowledge, this is the first study identifying unique physical attributes of cell populations generated during CAR-T cell product manufacturing that can be used to monitor or predict quality of the resulting therapeutic product.

Laid groundwork for validated in-line process analytics leveraging label-free CQAs of CAR-T cell products

Demonstrated analysis and “sorting” of qualified donor cells and/or engineered cells to identify and select rapidly for critical quality attributes (CQAs) defining safety and efficacy

Established validated set of label-free CQAs for CAR-T cell, which industry can use to correlate with preclinical and clinical results

Value Statement/Outcomes

This project demonstrated label‑free optical and microfluidic analytics that improves in‑line CQA assessment for drug companies, resulting in quality benefits across CAR‑T cell manufacturing.

Outputs/Deliverables

Label-free physical analysis of donor cells obtained at distinct manufacturing process steps, requiring adaptation of microfluidic and optical device-based assays.

Bio p hysical a ttribute d atabase ( PAD ) and b iological a ttribute d atabase ( BAD )

Regression model and identification of at least two candidate CQAs

Posters

Van Vliet, K. & Hebert, C., Label-free Critical Quality Attributes of T-cell Therapy Products, NIIMBL National Meeting, Washington, D.C., July 14, 2021.

Presentations

Van Vliet, K. & Hebert, C., Label-free Critical Quality Attributes of T-cell Therapy Products, NIIMBL Member Forum, Virtual, July 23, 2020.

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Project Lead

Massachusetts Institute of Technology

Massachusetts Institute of Technology

Participating Organizations

Bristol-Myers Squibb

Bristol-Myers Squibb

LumaCyte

LumaCyte