Premium
Scaffold‐Mediated Static Transduction of T Cells for CAR‐T Cell Therapy
Author(s) -
Agarwalla Pritha,
Ogunnaike Edikan A.,
Ahn Sarah,
Ligler Frances S.,
Dotti Gianpietro,
Brudno Yevgeny
Publication year - 2020
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202000275
Subject(s) - transduction (biophysics) , chimeric antigen receptor , scaffold , t cell , genetic enhancement , cell therapy , cd19 , microbiology and biotechnology , cell , viral vector , biology , antigen , immunology , gene , immune system , medicine , stem cell , biomedical engineering , biophysics , recombinant dna , biochemistry
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.