Nanocarriers for cancer nano-immunotherapy

Abstract

The host immune system possesses an intrinsic ability to target and kill cancer cells in a specific and adaptable manner that can be further enhanced by cancer immunotherapy, which aims to train the immune system to boost the antitumor immune response. Several different categories of cancer immunotherapy have emerged as new standard cancer therapies in the clinic, including cancer vaccines, immune checkpoint inhibitors, adoptive T cell therapy, and oncolytic virus therapy. Despite the remarkable survival benefit for a subset of patients, the low response rate and immunotoxicity remain the major challenges for current cancer immunotherapy. Over the last few decades, nanomedicine has been intensively investigated with great enthusiasm, leading to marked advancements in nanoparticle platforms and nanoengineering technology. Advances in nanomedicine and immunotherapy have also led to the emergence of a nascent research field of nano-immunotherapy, which aims to realize the full therapeutic potential of immunotherapy with the aid of nanomedicine. In particular, nanocarriers present an exciting opportunity in immuno-oncology to boost the activity, increase specificity, decrease toxicity, and sustain the antitumor efficacy of immunological agents by potentiating immunostimulatory activity and favorably modulating pharmacological properties. This review discusses the potential of nanocarriers for cancer immunotherapy and introduces preclinical studies designed to improve clinical cancer immunotherapy modalities using nanocarrier-based engineering approaches. It also discusses the potential of nanocarriers to address the challenges currently faced by immuno-oncology as well as the challenges for their translation to clinical applications.

Keywords: Cancer; Delivery; Immunotherapy; Nano-immunotherapy; Nanomedicine; Nanoparticle.

Fig. 1

The cancer–immunity cycle. Adapted from reference [23] with permission

Fig. 2

General approaches for nanocarrier-based modulation of the antitumor immune responses

Fig. 3

Antitumor mechanism of A cancer vaccine, B immune checkpoint inhibitor, C adoptive T cell therapy, and D oncolytic virus therapy

Fig. 4

In situ lymph node targeting and vaccine delivery via albumin “hitchhiking” approach. A The design of amphiphilic vaccines (amph-vaccines) that form micellar nanocarrier structure with an albumin-binding lipid tail. B Ex vivo fluorescence images of axillary and inguinal lymph nodes taken using fluorescently labeled CpG adjuvants and the corresponding fluorescence intensity at 24 h post-injection. C Immunohistochemistry of inguinal lymph nodes at 24 h post-injection. D Average growth curves of TC-1 tumors in C57BL/6 mice. Adapted from reference [65] with permission

Fig. 5

T cell “backpacking” with nanocarriers. A Multilamellar lipid nanoparticles carrying IL-15 super-agonist and IL-21 cytokines were chemically attached on T cells via maleimide-thiol reaction. B In vivo bioluminescence signal of adoptively transferred Pmel-1 T cells (left) and the survival rate of C57BL/6 mice bearing B16 melanoma after adoptive T cell therapy (right). C Synthesis of protein nanogels by reduction-sensitive crosslinking of IL-15 super-agonist cytokines. D In vitro T cell expansion over 12 days after stimulation with anti-CD3/CD28 antibodies. E Average growth curves of B16F10 tumors in C57BL/6 mice, and F the resulting survival rate of C57BL/6 mice. Adapted from references [114] and [115] with permission