Editors' ChoiceImmunotherapy

T cells in a (polymer) matrix

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Science Translational Medicine  04 Feb 2015:
Vol. 7, Issue 273, pp. 273ec21
DOI: 10.1126/scitranslmed.aaa5559

It is no secret that engineered T cells are the hot newcomers to the field of cancer immunotherapy. In recent months, several new companies have formed or joined academic centers to develop engineered T cells as commercially available clinical products. Although engineered T cells are a platform therapy that could be applied to multiple cancer types, most of the exciting clinical data have been in hematologic malignancies. One big question in the field is how well engineered T cells will traffic to and effect responses in solid tumors.

Now, Stephan et al. demonstrate that the antitumor potency of antigen-specific T cells can be improved substantially by embedding the T cells in a polymer matrix placed in the tumor bed or cavity. The scaffold is composed of a naturally occurring polysaccharide, alginate, coated with a collagen-mimetic peptide that binds lymphocytes. The matrix can also be coated with proteins that enhance T cell function, including agonistic antibodies to CD3, CD28, and 4-1BB and/or enhancing cytokines such as IL-15/IL-15Ra complexes. The scaffold therefore acts as an active reservoir that enhances T cell function and slowly releases the T cells locally as the material degrades. In two mouse models of cancer, T cells delivered in a matrix were more effective than local or intravenous delivery.

One outstanding question will be how to quickly generate T cells that are specific for the tumor; perhaps embedding checkpoint-blocking antibodies into the matrix will enhance the function of naturally occurring tumor-infiltrating lymphocytes. In any case, the combination of a bioengineering/biomaterial approach with a biologic approach has great potential to maximize the potency of immunotherapy for cancer.

S. B. Stephan et al., Biopolymer implants enhance the efficacy of adoptive T-cell therapy. Nat. Biotechnol. 10.1038/nbt.3104 (2015). [Abstract]

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