Delivery strategies of cancer immunotherapy: recent advances and future perspectives

Abstract

Immunotherapy has become an emerging strategy for the treatment of cancer. Immunotherapeutic drugs have been increasing for clinical treatment. Despite significant advances in immunotherapy, the clinical application of immunotherapy for cancer patients has some challenges associated with safety and efficacy, including autoimmune reactions, cytokine release syndrome, and vascular leak syndrome. Novel strategies, particularly improved delivery strategies, including nanoparticles, scaffolds, and hydrogels, are able to effectively target tumors and/or immune cells of interest, increase the accumulation of immunotherapies within the lesion, and reduce off-target effects. Here, we briefly describe five major types of cancer immunotherapy, including their clinical status, strengths, and weaknesses. Then, we introduce novel delivery strategies, such as nanoparticle-based delivery of immunotherapy, implantable scaffolds, injectable biomaterials for immunotherapy, and matrix-binding molecular conjugates, which can improve the efficacy and safety of immunotherapies. Also, the limitations of novel delivery strategies and challenges of clinical translation are discussed.

Implantable and Injectable Biomaterial Scaffolds for Cancer Immunotherapy

“…The research on the combination of biomaterials and immunotherapy are rapidly advancing to break the scientific barriers, and overcoming present immunotherapy deficiencies (Eppler and Jewell, 2020;Scheetz et al, 2019). Among these, implantable and injectable biomaterial scaffolds present a promising potential for biomaterial delivery systems (Zhao et al, 2019). The low accumulation and expansion of tumor-reactive lymphocytes at the tumor sites, and the complex procedure significantly impact the therapeutic effect of adoptive cellular immunotherapy (Beatty and Gladney, 2015).…”

“…Immunotherapy has five main classes: immune checkpoint blockade (ICB) therapy, lymphocytepromoting cytokine therapy, chimeric antigen receptor T-cell (CAR-T) therapy, agonistic antibodies, and tumor vaccines (Zhao et al, 2019). Among these, ICB therapy is the most comprehensively studied class of immunotherapy till now (López-Soto et al, 2017).…”

Clinical implication of cellular vaccine in glioma: current advances and future prospects

“…The first conceptual challenge is the choice of individualized neoantigen to be targeted and the accurate status assessment of such targets [ 143 ]. As more and more tumor neoantigens have been identified, the future fields of investigation should focus on the effective neoepitope dosage without tolerization and finding the best neoepitope delivery system [ 144 ]. In BALB/c mice, using a potent immunostimulatory adjuvant and delivery system for neoepitope immunization might be of great benefit to induce the CD8 + T cells-mediated tumor rejection response [ 145 ].…”

RNA sequencing: new technologies and applications in cancer research

“…Immunotherapies, especially immune checkpoint blockade (ICB), has opened a new chapter for anti-cancer therapy with remarkable responses from targeting programmed death 1 (PD1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) [146][147][148]. However, only a few patients benefit from ICB, and severe side effects were observed [149,150].…”