Scaffold-Mediated Static Transduction of T Cells for CAR-T Cell Therapy.
Pritha AgarwallaEdikan A OgunnaikeSarah AhnFrances S LiglerGianpietro DottiYevgeny BrudnoPublished in: Advanced healthcare materials (2020)
Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive clinical responses in patients with B-cell malignancies. Critical to the success of CAR-T cell therapies is the achievement of robust gene transfer into T cells mediated by viral vectors such as gamma-retroviral vectors. However, current methodologies of retroviral gene transfer rely on spinoculation and the use of retronectin, which may limit the implementation of cost-effective CAR-T cell therapies. Herein, a low-cost, tunable, macroporous, alginate scaffold that transduces T cells with retroviral vectors under static condition is described. CAR-T cells produced by macroporous scaffold-mediated viral transduction exhibit >60% CAR expression, retain effector phenotype, expand to clinically relevant cell numbers, and eradicate CD19+ lymphoma in vivo. Efficient transduction is dependent on scaffold macroporosity. Taken together, the data show that macroporous alginate scaffolds serve as an attractive alternative to current transduction protocols and have high potential for clinical translation to genetically modify T cells for adoptive cellular therapy.
Keyphrases
- cell therapy
- tissue engineering
- stem cells
- mesenchymal stem cells
- low cost
- sars cov
- copy number
- primary care
- genome wide
- healthcare
- poor prognosis
- gene therapy
- immune response
- dendritic cells
- gene expression
- genome wide identification
- regulatory t cells
- quality improvement
- long non coding rna
- diffuse large b cell lymphoma
- big data
- binding protein
- wound healing
- quantum dots
- transcription factor
- deep learning