Mimetic Heat Shock Protein Mediated Immune Process to Enhance Cancer Immunotherapy.

Inspired by heat shock proteins (HSPs), a self-assembly nanochaperone (nChap) is developed as a novel nanovaccine for boosting antitumor immune responses. Taking advantage of HSP-like microdomains and surface-decorated mannose, this nChap can efficiently capture antigens and ferry them into the dendritic cells (DCs). Subsequently, the nChap can blast lysosomes by transforming the structure and property of surface microdomains, thereby promoting antigen escape and enhancing their cross-presentation in cytoplasm. As a result, the nChap-based nanovaccine can elicit both CD4+ and CD8+ T cell-based immune responses and shows an excellent preventive effect on melanoma. Further combination of the nanovaccine with antiprogrammed death-1 (anti-PD-1) checkpoint blockade offers effective inhibition on the growth of already-established melanoma. Therefore, this nC ap-based nanovaccine provides a simple and robust strategy in mimicking HSPs to realize structure-assisted antigen capture, surface-receptor-mediated DC internalization, and both activation of humoral immunity and cellular immunity, promising for efficient cancer immunotherapy.

Endolysosomal-Escape Nanovaccines through Adjuvant-Induced Tumor Antigen Assembly for Enhanced Effector CD8+ T Cell Activation.

The activation of tumor-specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight-forward strategy of adjuvant-induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed. The resulting functionalizable nanovaccines are equipped with a pH (low) insertion peptide (pHLIP) to facilitate endolysosomal escape and to promote cytoplasmic localization, with the aim to enhance cross-presentation of the antigen by dendritic cells to effectively activate CD8+ T cell. The results demonstrate that pHLIP-functionalized model nanovaccine can induce endolysosomal escape and enhance CD8+ T cell activation both in vitro and in vivo. Furthermore, based on the adjuvant-induced antigen assembly, nanovaccines of the clinically relevant tumor-associated antigen NY-ESO-1 are generated and show excellent capacity to elicit NY-ESO-1-specific CD8+ T cell activation, demonstrating a high potential of this functionalizable nanovaccine formulation strategy for clinical applications.

Engineered Cancer Nanovaccines: A New Frontier in Cancer Therapy.

Vaccinations are essential for preventing and treating disease, especially cancer nanovaccines, which have gained considerable interest recently for their strong anti-tumor immune capabilities. Vaccines can prompt the immune system to generate antibodies and activate various immune cells, leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and surgery. To enhance the flexibility and targeting of vaccines, nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level, enabling more controlled and precise drug delivery to enhance immune responses. Cancer nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within nanomaterials. The small size of these nanomaterials allows for precise targeting of T cells, dendritic cells, or cancer cells, thereby eliciting a more potent anti-tumor response. In this paper, we focus on the classification of carriers for cancer nanovaccines, the roles of different target cells, and clinically tested cancer nanovaccines, discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation, while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy.

Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer α-mangostin (αM) into tumor cells through poly(d, l-lactide-co-glycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (αM-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, αM-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, αM-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assembled efficiently through this platform are promising for desirable cancer immunotherapy.

Advances in Cancer Nanovaccines: Harnessing Nanotechnology for Broadening Cancer Immune Response.

Many advances have been made recently in the field of cancer immunotherapy, particularly with the development of treatments such as immune checkpoint inhibitors and adoptive cellular immunotherapy. The efficacy of immunotherapy is limited, however, owing to high levels of tumor heterogeneity and the immunosuppressive environments of advanced malignant tumors. Therefore, therapeutic anticancer vaccines have gradually become powerful tools for inducing valid antitumor immune responses and regulating the immune microenvironment. Tumor vaccines loaded in nanocarriers have become an indispensable delivery platform for tumor treatment because of their enhanced stability, targeting capability, and high level of safety. Through a unique design, cancer nanovaccines activate innate immunity and tumor-specific immunity simultaneously. For example, the design of cancer vaccines can incorporate strategies such as enhancing the stability and targeting of tumor antigens, combining effective adjuvants, cytokines, and immune microenvironment regulators, and promoting the maturation and cross-presentation of antigen-presenting cells (APCs). In this review, we discuss the design and preparation of nanovaccines for remodeling tumor antigen immunogenicity and regulating the immunosuppressive microenvironment.

Emerging advances in nanomedicine for breast cancer immunotherapy: opportunities and challenges.

Breast cancer is one of the most common causes of cancer-related morbidity and mortality in women worldwide. Early diagnosis and an appropriate therapeutic approach for all cancers are climacterics for a favorable prognosis. Targeting the immune system in breast cancer is already a clinical reality with notable successes, specifically with checkpoint blockade antibodies and chimeric antigen receptor T-cell therapy. However, there have been inevitable setbacks in the clinical application of cancer immunotherapy, including inadequate immune responses due to insufficient delivery of immunostimulants to immune cells and uncontrolled immune system modulation. Rapid advancements and new evidence have suggested that nanomedicine-based immunotherapy may be a viable option for treating breast cancer.

Cancer that begins in the breast is referred to as breast cancer. It may originate in either one or both breasts. It is one of the main causes of cancer-related death among women worldwide. Cancer immunotherapy is a game-changing treatment that improves the ability of the host defense system to spot and eliminate cancer cells with pinpoint accuracy. Cancer immunotherapy, also referred to as immuno-oncology, is a type of treatment option for breast cancer that uses the body's natural defense system to prevent, regulate and eliminate breast cancer. Immunotherapy is used to enhance or alter the functioning of the immune system so that it can locate and destroy cancer cells. Knowing how immunotherapy works and what to anticipate can often offer peace of mind to the patient who can then make informed decisions about care, especially if immunotherapy is part of the treatment plan for a particular patient.