Engineered Multifunctional Nano‐ and Biological Materials for Cancer Immunotherapy

Abstract

Cancer immunotherapy is set to emerge as the future of cancer therapy. However, recent immunotherapy trials in different cancers have yielded sub‐optimal results, with durable responses seen in only a small fraction of patients. Engineered multifunctional nanomaterials and biological materials are versatile platforms that can elicit strong immune responses and improve anti‐cancer efficacy when applied to cancer immunotherapy. While there are traditional systems such as polymer‐ and lipid‐based nanoparticles, there is a wide variety of other materials with inherent and additive properties that can allow for more potent activation of the immune system. By synthesizing and applying multifunctional strategies, it allows for a more extensive and more effective repertoire of tools to use in the wide variety of situations that cancer presents itself. Here, several types of nanoscale and biological material strategies and platforms that provide their inherent benefits for targeting and activating multiple aspects of the immune system are discussed. Overall, this review aims to provide a comprehensive understanding of recent advances in the field of multifunctional cancer immunotherapy and trends that pave the way for more diverse and tactical regression of tumors through soliciting responses by either the adaptive or innate immune system, and even both simultaneously.

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

“…ACT has provided modest therapeutic efficacy in treating common epithelial cancer due to enhanced T cell functionalization in the TME of solid tumors. CAR-T cells have been approved by the FDA for application of CD19 targeted CAR-T cells of B cell leukemia and lymphoma . A genetically engineered class of ACT, CAR-T cells are modified by single chain variable fragments of antibodies which retain certain T cell receptors and T cell stimulatory domains for enhanced immune response.…”

“…CAR-T cells have been approved by the FDA for application of CD19 targeted CAR-T cells of B cell leukemia and lymphoma. 125 A genetically engineered class of ACT, CAR-T cells are modified by single chain variable fragments of antibodies which retain certain T cell receptors and T cell stimulatory domains for enhanced immune response. Tumor-infiltrating lymphocytes (TILs) encompass antitumoral TILs obtained from tumor sites with immune memory, which passes in vitro expansion and then are injected back into the body for expansion.…”

Stepwise Size Shrinkage Cascade‐Activated Supramolecular Prodrug Boosts Antitumor Immunity by Eliciting Pyroptosis

“…Current nanodelivery systems can partially address these issues. [ 11 ] For example, clinically approved PEGylated liposomal doxorubicin (Doxil) effectively enhanced tumor accumulation and relieved adverse effects. [ 12 ] However, the therapeutic outcomes show no considerable improvements compared to monotherapy.…”

Evaluation of Cellular Targeting by Fab′ vs Full-Length Antibodies in Antibody–Nanoparticle Conjugates (ANCs) Using CD4 T-cells

“…The smaller size of Fab′ confers additional advantages over full-length antibody 21 such as ease of production in microbial systems 22 (libraries generated via phage display 23 ), higher penetration depths in solid tumors, 24 and minimized off-target interaction with Fc-receptor bearing immune cells. 25 Consequently, many antibody fragments have entered the clinical trials with three FDA-approved Fabs in the market today. 26 Due to the presence of unique receptors on immune cells such as with CD19/CD22 on B-cells and CD30 on T-cells, there are currently three FDA approved antibody−drug conjugates that are successful in the treatment of B/T-cell malignancies.…”

“…This was carried out in three steps: (a) obtaining the antigen-binding domain with an intact thiol (Fab′) from the full-length antibody in two steps, (b) formulating a nanoparticle system with a chemical handle for bioconjugation, and (c) installing the targeting antibody on the nanoparticle using a strain-promoted alkyne–azide cycloaddition (SPAAC) reaction. The smaller size of Fab′ confers additional advantages over full-length antibody such as ease of production in microbial systems (libraries generated via phage display), higher penetration depths in solid tumors, and minimized off-target interaction with Fc-receptor bearing immune cells . Consequently, many antibody fragments have entered the clinical trials with three FDA-approved Fabs in the market today …”