Adu-Berchie et al. tested a biomaterial platform – synergistic in situ vaccination enhanced T cell depot (SIVET) – for local delivery of T cells to tumor sites to improve adoptive T cell therapy. The hydrogel was constructed to release FLT3L or GM-CSF to recruit APCs, and CpG to activate recruited APCs. This approach increased tumoral levels of non-exhausted T cells, improved transferred T cell persistence, and induced infiltration of host T cells and myeloid cells with activation and antigen-presenting characteristics. Furthermore, the SIVET approach was shown to induce long-term memory responses and protect against tumor antigen escape.
Contributed by Maartje Wouters
ABSTRACT: Although adoptive T cell therapy provides the T cell pool needed for immediate tumor debulking, the infused T cells generally have a narrow repertoire for antigen recognition and limited ability for long-term protection. Here, we present a hydrogel that locally delivers adoptively transferred T cells to the tumor site while recruiting and activating host antigen-presenting cells with GMCSF or FLT3L and CpG, respectively. T cells alone loaded into these localized cell depots provided significantly better control of subcutaneous B16-F10 tumors than T cells delivered through direct peritumoral injection or intravenous infusion. T cell delivery combined with biomaterial-driven accumulation and activation of host immune cells prolonged the activation of the delivered T cells, minimized host T cell exhaustion, and enabled long-term tumor control. These findings highlight how this integrated approach provide both immediate tumor debulking and long-term protection against solid tumors, including against tumor antigen escape.
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. The Wyss Institute for Biologically Inspired Engineering Harvard University,
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (2) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (3) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (4) The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (5) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (6) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (7) The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (8) The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (9) The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (10) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (11) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. (12) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. mooneyd@seas.harvard.edu. The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, USA. mooneyd@seas.harvard.edu.
