Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy

Abstract

Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl). In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia, cisplatin, radiotherapy or photodynamic therapy. To improve HOCl-CDS activity at the tumor site, we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold. When injected intratumorally, the HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration, and tumor-associated macrophage reprogramming towards an M1 phenotype. The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16–F10 melanoma. Furthermore, hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade. These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.

New advances in pharmaceutical strategies for sensitizing anti‐PD‐1 immunotherapy and clinical research

“…It is necessary to use highly biocompatible materials to effectively encapsulate antigens and adjuvants to prevent burst release, achieve controlled release and optimize the efficacy. Additionally, it is meaningful to target delivery to APCs to induce effective antitumor T cells reaction (Y. Zhou et al, 2022). Because DCs are the most important APCs, increasing the uptake, processing and delivery of antigens by DCs is an effective means to improve the outcome of cancer vaccines.…”

“…Additionally, it is meaningful to target delivery to APCs to induce effective antitumor T cells reaction (Y. Zhou et al, 2022). Because DCs are the most important APCs, increasing the uptake, processing and F I G U R E 1 3 Schematic illustration of the plasma membrane (PM)-targeted PDT (PM-PDT) combined with PD-1 checkpoint blockade therapy for eradicating primary tumors and inhibiting distant tumors (C. Zhang, Gao, et al, 2019).…”

A Simple Self-assembling System of Melittin for Hepatoma Treatment

“…Shielding the positive charge of melittin is crucial for decreasing the interaction with RBCs. [11] Furthermore, after self-assembly into M/VG nanoparticles, the α-helical melittin changed into a random coil, probably yielding a decreased hemolytic effect of melittin (Fig. 4E).…”

“…and hydrogels [11]. Modi cation or complex multifunctional carriers are often limited by the complexity of the production process, high cost, and repeatability, which hinder their clinical applications.…”

A simple self-assembling system of melittin for hepatoma treatment

“…The first is chemical modification to increase specificity and decrease hemolysis (Lyu et al 2018;Ventura and Wiedman 2021). The second is physicochemical encapsulation by various nanocarriers, such as classical liposomes (Mao et al 2017), polyelectrolyte nanocarriers (Motiei et al 2021), polymeric nanocarriers (Lv et al 2021), redox-sensitive nanocomplexes (Cheng and Xu 2020), pH-sensitive micelles (Peeler et al 2019), microneedles (Du et al 2021), inorganic materials (Li et al 2018), and hydrogels (Zhou et al 2021a). Modification or complex multifunctional carriers are often limited by the complexity of the production process, high cost, and repeatability, which hinder their clinical applications.…”