Editors' ChoiceCancer

It’s what’s inside that counts for nanoparticle vaccines

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Science Translational Medicine  22 Nov 2017:
Vol. 9, Issue 417, eaar2438
DOI: 10.1126/scitranslmed.aar2438

Abstract

Plasma membranes of tumor cells induce antitumor immunity when wrapped around a nanoformulated CpG adjuvant.

Cancer vaccine strategies based on triggering immunity through tumor antigen exposure have a long and challenging history of clinical translation. Autologous tumor cell vaccines composed of tumor cells isolated from a patient that are irradiated, mixed with an immunostimulatory adjuvant such as bacille Calmette-Guérin, and reinjected into the patient, have been clinically tested at least since the 1970s. Unfortunately, the immunosuppressive microenvironment typically associated with many cancers has limited the clinical efficacy of these vaccines. The success of immune checkpoint blockade therapy, using antibodies targeting programmed death receptor–1 (PD-1) and cytotoxic T lymphocyte antigen–4 (CTLA4), now offers a proven strategy for reducing tumor immunosuppression. However, immune checkpoint blockade often fails in patients with poorly immunogenic tumors. Thus, the possibility of combining immune checkpoint blockade with an immunostimulatory tumor cell vaccine has emerged as an opportune therapy in the field.

In this context, Kroll and colleagues revisit the tumor cell vaccine approach and apply concepts of biomimetic nanotechnology to improve efficacy. Several features define their strategy: (i) a polymeric nanoparticle (NP)-based platform roughly 150 nm in diameter is used to efficiently deliver material to antigen-presenting cells (APCs), including dendritic cells and macrophages; (ii) NPs are coated in tumor cell membranes extracted by ultracentrifugation, to mimic the structure of the tumor cell surface and thus to preserve and present a natural ensemble of multiple tumor antigens; and (iii) CpG oligonucleotide, which serves as an immunostimutory adjuvant that engages toll-like receptor 9 on APCs, is encapsulated within the NPs. The NPs accumulated in APCs of the draining lymph node after subcutaneous injection in mice. Nanoformulation of CpG more efficiently induced immunostimulation and dendritic cell maturation compared with free CpG. The approach also led to more effective subsequent in vivo T cell response compared with various comparators, including vaccines based on whole-cell lysate, free CpG, NPs lacking CpG but containing tumor cell membranes, and combinations thereof.

The NP platform outperformed the same comparators in tests of prophylactic immunization, such that NP treatment prior to tumor implantation (using the same tumor cell line from which the vaccine was derived) prevented tumor growth. These experiments demonstrated that CpG encapsulation within cell membrane–coated NPs was important for efficacy; although dual treatment with particles individually containing either CpG or cell membranes was not tested. In a more clinically relevant test as a therapeutic autologous tumor cell vaccine, the NP platform eliminated established tumors in mice when combined with anti-PD1 and anti-CTLA4 antibody therapy.

Because this NP platform relies on cell-membrane isolation, there may be practical limitations that impede clinical adoption of autologous-based treatment. Nonetheless, although efficacy was not tested in allogeneic models, the authors provide compelling evidence that encapsulating vaccine adjuvant in tumor-cell mimetic nanoparticles can be an effective and efficient method of inducing immunity.

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