In Situ Dendritic Cell Vaccine for Effective Cancer Immunotherapy

Abstract

A cancer vaccine is an important form of immunotherapy. Given their effectiveness for antigen processing and presentation, dendritic cells (DCs) have been exploited in the development of a therapeutic vaccine. Herein, a versatile polymersomal nanoformulation that enables generation of tumor-associated antigens (TAAs) and simultaneously serves as adjuvant for an in situ DC vaccine is reported. The chimeric cross-linked polymersome (CCPS) is acquired from self-assembly of a triblock copolymer, polyethylene glycol-poly­(methyl methyacrylate-co-2-amino ethyl methacrylate (thiol/amine))-poly 2-(dimethylamino)­ethyl methacrylate (PEG-P­(MMA-co-AEMA (SH/NH2)-PDMA). CCPS can encapsulate low-dose doxorubicin hydrochloride (DOX) to induce immunogenic cell death (ICD) and 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), a photosensitizer to facilitate photodynamic therapy (PDT) for reactive oxygen species (ROS) generation. This combination is able to enhance the population of TAAs and DC recruitment, eliciting an immune response cascade. In addition, CCPS with primary and tertiary amines act as adjuvant, both of which can stimulate DCs recruited to form an in situ DC vaccine after combination with TAAs for MC38 colorectal cancer treatment. In vivo results indicate that the all-in-one polymersomal nanoformulation (CCPS/HPPH/DOX) increases mature DCs in tumor-draining lymph nodes (tdLNs) and CD8+ T cells in tumor tissues to inhibit primary and distant MC38 tumor growth following a single intravenous injection with a low dose of DOX and HPPH.

A Multifunctional Cascade Bioreactor Based on Hollow‐Structured Cu2MoS4 for Synergetic Cancer Chemo‐Dynamic Therapy/Starvation Therapy/Phototherapy/Immunotherapy with Remarkably Enhanced Efficacy

“…After the synergistic comprehensive treatment, the dying cancer cells could release tumor‐associated antigens (TDPAs), which could disperse into the lower chamber and remarkably induce DCs maturation. The DCs were stained with T lymphocyte receptors CD28 bind costimulatory molecules (CD80, CD86), which is quite important index in eliciting T cell‐mediated immune responses as hallmarks for DC maturation . As shown in the flow cytometry analysis (Figure E), the PEGylated CMS@GOx nanomedicine in combination with 1064 nm laser irradiation could significantly induce in vitro DC maturation.…”

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

“…Chimeric cross-linked polymersomes (CCPS) with co-encapsulated Dox and 2-(1-hexyloxyethyl)-2devinyl pyropheophorbide-a (HPPH) as photosensitizer (CCPS/HPPH/Dox) were tested to develop an in situ DC vaccination using copolymers as adjuvants combined with TAAs for MC38 colorectal cancer treatment. A single low-dose administration of this Dox and HPPT combination could inhibit primary and distant MC38 tumor growth [71]. PDT has been associated with expression of several DAMPs that are involved in ICD, as reported above.…”

“…The accumulated experimental evidence strongly supports the idea that in situ DC vaccination benefits from tumor pretreatment with pro-apoptotic agents [64,67,68] and, in particular, with ICD inducers. In fact, in vivo employment of ICD inducers results not only in TAA release by dying cells, but also in the secretion of DC activating DAMPs and more efficient engulfment of tumor cells by DCs [57,58,[69][70][71].…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…A safe and effective immunotherapy with great controllability and sensitivity can be achieved by developing novel drug delivery platforms based on nanotechnology and material science. [264][265][266][267][268][269][270] The cascaded synergistic effects of photodynamic-immunotherapy can provide a promising strategy to inhibit both primary lesions and distant metastases, which can be hardly achieved by conventional PDT with limited immunologic effects. [256] Moreover, the combination of immunotherapy and PDT has attracted an increasing attention due to the potential systematic antitumor immunity after PDT.…”