Antibody-Immobilized < wbr > Nanofiber Scaffolds for the Delivery of Human Tumor Antigen-Specific Cytotoxic T Lymphocytes

Abstract

Adoptive cell therapy (ACT) employing the transfer of ex vivo expanded effector cells is an attractive approach for cancer treatment. The successful clinical translation of ACT, however, is impeded by inadequate effector cell numbers and poor persistence after infusion. To circumvent these limitations, we propose the use of biocompatible poly (lactide-co-glycolide) (PLGA) nanofiber scaffolds as a platform to effectively deliver human tumor antigen-specific cytotoxic T lymphocytes (CTLs) directly to the tumor site. We modified the PLGA nanofiber scaffolds with monoclonal antibodies (anti-CD8 and anti-CD28 Abs) to provide adhesion and co-stimulatory signals to CTLs. We show that CTLs can be attached and gradually released from the nanofiber scaffolds. We found that the nanofiber scaffold-released CTLs are more activated, have higher CD28 expression, and exhibit higher cytotoxicity with elevated IFNg production, compared to CTLs expanded in a conventional rapid expansion protocol. Our data highlight that anti-CD8/anti-CD28 Ab-conjugated PLGA nanofiber scaffolds can provide a biocompatible biodegradable delivery platform of tumor-specific CTLs by providing T cell persistence and tumor cytolytic function in the patients. Therefore, nanofiber scaffolds incorporated with have become potentially be a more successful strategy for ACT.