Background: Inspired by nature, the biomimetic approach has been incorporated into drug nanocarriers for cancer targeted chemotherapy. The nanocarriers are cloaked in cell membranes, which enables them to incorporate the functions of natural cells.Key scientific concepts of review: Nanocarriers surface engineered with cell membranes have emerged as a fascinating source of materials for cancer targeted chemotherapy. A distinctive characteristic of cell membrane-coated nanocarriers (CMCNs) is that they include carbohydrates, proteins, and lipids, in addition to being biocompatible. CMCNs are capable of interacting with the complicated biological milieu of the tumor because they contain the signaling networks and intrinsic functions of their parent cells. Numerous cell membranes have been investigated for the purpose of masking nanocarriers with membranes, and various tumor-targeting methods have been devised to improve cancer targeted chemotherapy. Moreover, the diverse structure of the membrane from different cell sources broadens the spectrum of CMCNs and offers an entirely new class of drug-delivery systems.Aim of review: This review will describe the manufacturing processes for CMCNs and the therapeutic uses for different kinds of cell membrane-coated nanocarrier-based drug delivery systems, as well as addressing obstacles and future prospects.Graphical

Hyaluronidase (HAase), a family of enzymes critical for regulating physiological and pathological states, catalyzes the degradation of hyaluronic acid (HA), a key component of the extracellular matrix (ECM). By modulating ECM composition and cellular signaling pathways, HAase plays a pivotal role in diverse biological processes, including wound healing, tissue regeneration, and tumor progression. This review systematically elucidates the classification, biological sources, structural diversity, and catalytic mechanisms of HAase, emphasizing its dynamic involvement in disease pathogenesis and diagnostic potential. Furthermore, the article explores innovative therapeutic strategies centered on HAase modulation. HAase inhibitors emerge as promising tools for maintaining HA homeostasis, with implications in anti-inflammatory, antimicrobial, and antitumor therapies by blocking excessive HA degradation. Concurrently, HAase-mediated drug delivery systems represent a paradigm shift in overcoming biological barriers, enhancing bioavailability, and optimizing therapeutic outcomes through ECM remodeling. Notably, the synergy between HAase and immunotherapeutic modalities, such as checkpoint inhibitors and adoptive cell therapies, demonstrates synergistic antitumor effects by reshaping the tumor microenvironment (TME) and augmenting immune cell infiltration. Nevertheless, numerous challenges persist in the clinical application of hyaluronidase, including its immunogenicity, safety, application limitations and ethical considerations. This review synthesizes current research advances and unresolved issues, integrating molecular insights with translational perspectives, aiming to provide a more comprehensive and in-depth understanding of hyaluronidase and to advance clinical therapeutic strategies for hyaluronidase.

Squamous cell carcinomas are the most common head and neck malignancies. Significant progress has been made in standard therapeutic methods combining surgery, radiation, and chemotherapy. Nevertheless, the 5-year survival rate remains at 40–50%. Immune checkpoint inhibitors (ICIs) are a new strategy for treating head and neck squamous cell carcinomas (HNSCCs). Still, the overall response and effective rates are poor, as HNSCCs are ‘cold’ tumors with an immunosuppressive tumor microenvironment (TME), limiting ICI’s beneficial effects. In this case, transforming the tumor suppression microenvironment before using ICIs could be helpful. Oncolytic viruses (OVs) can transform cold tumors into hot tumors, improving the situation. Talimogene laherparepvec (T-VEC), oncolytic immunotherapy authorized for advanced melanoma, also showed good safety and antitumor activity in treating head and neck cancer and pancreatic cancer. In combination with pembrolizumab, T-Vec may have more anticancer efficacy than either drug alone. Therefore, understanding the mechanisms underpinning OVs and their potential synergism with ICIs could benefit patients with HNSCC.

Head and neck cancer (HNC), which includes lip and oral cavity, larynx, nasopharynx, oropharynx, and hypopharynx malignancies, is one of the most common cancers worldwide. Due to the interaction of tumor cells with immune cells in the tumor microenvironment, immunotherapy of HNCs, along with traditional treatments such as chemotherapy, radiotherapy, and surgery, has attracted much attention. Four main immunotherapy strategies in HNCs have been developed, including oncolytic viruses, monoclonal antibodies, chimeric antigen receptor T cells (CAR-T cells), and therapeutic vaccines. Oncorine (H101), an approved oncolytic adenovirus in China, is the pioneer of immunotherapy for the treatment of HNCs. Pembrolizumab and nivolumab are mAbs against PD-L1 that have been approved for recurrent and metastatic HNC patients. To date, several clinical trials using immunotherapy agents and their combination are under investigation. In this review, we summarize current the interaction of tumor cells with immune cells in the tumor microenvironment of HNCs, the main strategies that have been applied for immunotherapy of HNCs, obstacles that hinder the success of immunotherapies in patients with HNCs, as well as solutions for overcoming the challenges to enhance the response of HNCs to immunotherapies.

Oncolytic viruses have attracted attention as a promising strategy in cancer therapy owing to their ability to selectively infect and kill tumor cells, without affecting healthy cells. They also exert their anti-tumor effects by releasing immunostimulatory molecules from dying cancer cells. Several regulatory mechanisms, such as autophagy, contribute to the anti-tumor properties of oncolytic viruses. Autophagy is a conserved catabolic process in responses to various stresses, such as nutrient deprivation, hypoxia, and infection that produces energy by lysosomal degradation of intracellular contents. Autophagy can support infectivity and replication of the oncolytic virus and enhance their anti-tumor effects via mediating oncolysis, autophagic cell death, and immunogenic cell death. On the other hand, autophagy can reduce the cytotoxicity of oncolytic viruses by providing survival nutrients for tumor cells. In his review, we summarize various types of oncolytic viruses in clinical trials, their mechanism of action, and autophagy machinery. Furthermore, we precisely discuss the interaction between oncolytic viruses and autophagy in cancer therapy and their combinational effects on tumor cells.

Immunotherapy with CD19-targeting bispecific T-cell engagers (CD19BiTEs) has demonstrated highly effective killing of cancer cells in patients with precursor acute lymphoblastic leukemia and non-Hodgkin’s lymphomas. However, there are some drawbacks to this therapy, such as toxicity, short half-life in the serum, and immunosuppressive tumor microenvironment that could limit the use of CD19BiTEs in the clinic. Here, we generate an oncolytic vaccinia virus (OVV) encoding a CD19-specific BiTE (OVV-CD19BiTE). We demonstrate that OVV-CD19BiTE’s ability to replicate and induce oncolysis was similar to that of its parental counterpart. Supernatants from OVV-CD19BiTE-infected cells could induce activation and proliferation of human T cells, and the bystander effect of the virus was also demonstrated. In vivo study showed that OVV-CD19BiTE selectively replicated within tumor tissue, and contributed to a more significantly increased percentage of CD3, CD8, and naïve CD8 T subpopulations within tumors in contrast to blinatumomab. More importantly, treatment with OVV-CD19BiTE both in vitro and in vivo resulted in potent antitumor activity in comparison with control OVV or blinatumomab, a first-in-class BiTE, thereby resulting in long-term tumor remissions without relapse. The study provides strong evidence for the therapeutic benefits of CD19-targeting BiTE expression by OVV, and suggests the feasibility of testing the approach in clinical trials.