In Situ Tumor Vaccination with Calcium‐Linked Degradable Coacervate Nanocomplex Co‐Delivering Photosensitizer and TLR7/8 Agonist to Trigger Effective Anti‐Tumor Immune Responses

Abstract

In situ anti-tumor vaccination is an attractive type of cancer immunotherapy which relies on the effectiveness of dendritic cells (DCs) to engulf tumor antigens, become activated, and present antigens to T cells in lymphoid tissue. Here, a multifunctional nanocomplex based on calcium crosslinked polyaspartic acid conjugated to either a toll-like receptor (TLR)7/8 agonist or a photosensitizer is reported. Intratumoral administration of the nanocomplex followed by laser irradiation induces cell killing and hence generation of a pool of tumor-associated antigens, with concomitant promotion of DCs maturation and expansion of T cells in tumor-draining lymph nodes. Suppression of tumor growth is observed both at the primary site and at the distal site, thereby hinting at successful induction of an adaptive anti-tumor response. This strategy holds promise for therapeutic application in a pre-operative and post-operative setting to leverage to mutanome of the patient's own tumor to mount immunological memory to clear residual tumor cells and metastasis.

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

“…417,418 These results suggest that dying cancer cells releasing TAAs after phototherapy can induce adjuvant effects by stimulating an immune response, and thus, this strategy can be considered an "automatic vaccine". 419,420 For instance, a tumor cell membrane-modified Au nanoplatform (named C-RAuNC) was encapsulated with the ferroptosis agonist RSL3 and administered to prevent osteosarcoma drug resistance. 421 In this nanoplatform, RSL3 can inhibit glutathione peroxidase (GPX4) to mediate ferroptosis.…”

Research progress of nanovaccine in anti-tumor immunotherapy

“…The suppressive effects of the TME often result in reduced infiltration or dysfunction of immune cells such as DCs, and their defective function is one of the key factors responsible for tumor evasion of immune surveillance (146). In the TME, nanovaccines are an attractive tumor treatment that initiates the cancer immune cycle by inducing the immunogenic death of tumor cells and generating a rich pool of tumor antigens (147,148). Enhancing the function of DCs in response to the characteristics of the TME is crucial in tumor immunotherapy to transform "cold" tumors and metastasis into "hot" tumors (149).…”

The Role of Toll-like Receptor Agonists and Their Nanomedicines for Tumor Immunotherapy

“…Owing to various carboxyl groups in PASP, it could be crosslinked with calcium ions to form a pH-responsive nanocomplex. The system displayed that the repolarization of macrophages in TDLNs occurred as well as the proliferation and activity of CD4 + and CD8 + T cells in tumor sites, thus remarkably preventing tumor proliferation and metastasis [148]. Lin and colleagues reported dual-functional PLGA-ICG-R848 NPs in combination with PTT and immunotherapy for prostate cancer (PCa), promoting BMDCs maturation with the considerably increased proportions of CD11c + CD86 + and CD11c + CD80 + cells [152].…”