Biointerfacing Antagonizing T‐Cell Inhibitory Nanoparticles Potentiate Hepatocellular Carcinoma Checkpoint Blockade Therapy

Abstract

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies with few effective treatment options all around the world. The efficacy of the arisen immune checkpoint therapy is still uncertain due to local immunosuppression. In order to further overcome T cell suppression in the tumor immune microenvironment while promoting the immune response of antigen‐presenting cells, a biointerfacing antagonizing T‐cell inhibitory nanoparticles (BAT NPs) has been developed by cloaking platelet membrane on the PLGA microsphere surface to load T‐cell immunoglobulin domain and mucin domain‐3 antibodies (anti‐TIM‐3) as well as PD‐L1. Notably, in addition to activating the proliferation and migration of T cells, the contained anti‐TIM‐3 can cooperate with PD‐L1 checkpoint blockade to exert therapeutic effects. Furthermore, the components of BAT NPs like anti‐TIM‐3 and platelet can act together for collagen deposition in tumor starvation treatment. Thus, a novel targeting therapeutic strategy that can effectively reverse the immune‐inhibiting microenvironment is effectively applied to PD‐L1 checkpoint combination therapy. Such therapeutic effect can subsequently activate the effector T lymphocytes and antigen presentation of dendritic cells as well as the polarization of M1‐type macrophages. Last, the study presented the synergistic effect of immune therapeutic adjuvants and BAT NPs components in achieving tumor inhibition and prolonging tumor‐burden survival.

The immune response of hepatocellular carcinoma after locoregional and systemic therapies: The available combination option for immunotherapy

“…Previous research has established that there are biointerfacing antagonizing T-cell inhibitory nanoparticles (BAT NPs) for HCC, which were developed by cloaking the platelet membrane on the PLGA microsphere surface to load T-cell immunoglobulin domain and mucin domain-3 antibodies (anti-TIM-3) as well as PD-L1. This therapeutic effect could subsequently activate effector T lymphocytes and the polarization of M1-type macrophages as well as antigen presentation by dendritic cells (86). Finally, the relationship between the high expression of Tim-3 and the poor prognosis of HCC has been clearly confirmed, and it can regulate the microenvironment of stem cells and affect the regulation of the biological behavior of HCC.…”

Caveolin-mediated cytosolic delivery of spike nanoparticle enhances antitumor immunity of neoantigen vaccine for hepatocellular carcinoma

“…Moreover, because scVLPs have a similar morphology to virus that can be efficiently internalized into lymphocyte cells [40], they are considered to be one of the most efficient and promising vectors for the development of cancer immunotherapy vaccines. In addition, dysfunctional CD8 + T cells in the tumor microenvironment (TME) often upregulate inhibitory molecules including the T cell immunoglobulin and mucin domain (TIM-3) and programmed cell death protein 1 (PD-1) [41,42], to inhibit the magnitude of immune responses [43][44][45][46][47][48], while blocking such inhibitory signaling (such as TIM-3 signaling) is a promising strategy to rescue exhausted CD8 + T cells for counter immunotherapy resistance [49][50][51][52][53][54].…”