Researchers construct ionizable iron nanoadjuvant for personalized tumor vaccine treatment

Tumor vaccines represent a therapeutic method that can induce body-specific and persistent anti-tumor immune response, and have great prospects
for improving clinical tumor treatment.
However, the low immunogenicity of tumor antigens, low cytoplasmic delivery efficiency, and poor lymphoid organ targeting limit the level of anti-tumor immune response induced by tumor vaccines, which in turn leads to poor
clinical treatment effects.
The development of novel immune adjuvants provides a powerful strategy
to improve the efficacy of tumor vaccines.
As one of the most promising immune adjuvants, Stimulator of interferon genes (STING) signaling agonists stimulates the activation of STING signaling in antigen-presenting cells and induces the secretion of Type I interferon (IFN-I), thereby promoting the cross-presentation of tumor antigens and the proliferation and activation
of subsequent T lymphocytes 。 However, when free STING agonists participate in the design of tumor vaccines as immune adjuvants, there are still problems such as poor lymphoid organ delivery efficiency and inability to improve antigen cytosolic release, which is also one of the key reasons for the poor clinical treatment effect of the current water-soluble vaccine, that is, the physical mixture of
tumor antigen and immune adjuvant.
Therefore, the development of a new generation of vaccine preparations to synergistically promote the cytoplasmic delivery of tumor antigens and the efficient activation of STING signals in lymphoid organs is of great significance
for improving tumor vaccine treatment.

In response to the above challenges, Yu Haijun, a researcher at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, published a research paper entitled Acid-ionizable iron nanoadjuvant augments STING activation for personalized vaccination immunotherapy of cancer in Advanced Materials.
In this study, a library of ionizable iron nanoadjuvants was innovatively constructed to specifically amplify the activation
of STING signals in draining lymph nodes.
At the same time, nano-adjuvants can universally and efficiently deliver multiple forms of tumor antigens and induce strong and specific anti-tumor immune responses
in vivo.
This study demonstrates the promise
of ionizable iron nanoadjuvant for personalized tumor vaccine treatment.

The researchers demonstrated that iron oxide nanoparticles (IONPs), a clinically approved imaging contrast agent, can induce IFN-I mass secretion
by inducing intracellular reactive oxygen species to synergistically stimulate STING signaling activation with the STING agonist MSA-2.
They designed and synthesized a series of acid ionizable copolymers and self-assembled them through their electrostatic interactions with IONPs and MSA-2 to construct a library
of ionizable iron nanoadjuvants.
This nanoadjuvant efficiently drains and accumulates to lymph nodes, inducing significant expression of interferon-stimulating genes in lymph nodes
.
At the same time, the nano-adjuvant can be further used as a vaccine delivery vehicle to construct tumor nanovaccines
by self-assembly with the model antigen chicken egg albumin (OVA).
The nanovaccine not only activated STING signal in cascade, but also effectively promoted the cytoplasmic delivery of antigens, thereby achieving efficient antigen cross-presentation, and finally induced a nearly 170-fold increase in antigen-specific CD8+ T lymphocyte response, and showed significant tumor prevention and growth inhibition ability
in mouse B16OVA melanoma models.
In addition, the nanoadjuvant can also deliver autologous tumor cell membrane antigens obtained after surgical resection for postoperative tumor immunotherapy
.
The combination of nano-vaccine and immune checkpoint blocking therapy significantly inhibited the postoperative recurrence and distal metastasis of B16OVA and MC38 tumors, and induced long-term anti-tumor immune memory effects
.
Ionizable iron nanoadjuvants represent a powerful and universal vaccine delivery platform, which can improve the efficiency of tumor antigen cross-presentation and T lymphocyte activation, and provide a new strategy
for personalized tumor vaccine treatment.

The relevant research work has been funded
by the Key Research and Development Program of the Ministry of Science and Technology, the National Natural Science Foundation of China, and the International Cooperation Project of the Shanghai Municipal Science and Technology Commission.