Unleashing cell-penetrating peptide applications for immunotherapy

CPP conjugates can penetrate tissue barriers such as the blood–brain barrier and skin, that are difficult for other drugs to pass. CPP-conjugated antigen delivery in APCs or directly in vivo can increase the cytotoxic T lymphocyte (CTL) response as well as the antibody response by cross-presentation. CPP-conjugated cell fate controlling peptides or proteins can modulate lymphocyte function such as increasing regulatory T cell differentiation or inhibiting type 17 T helper cells to regulate autoimmunity, allergy, or organ transplantation. CPP-mediated molecular delivery for enhancing the type 1 T helper cell or CTL responses results in antitumor immunity and can enhance the efficacy of immune checkpoint inhibitors. There have been recent significant advances in clinical trials addressing human diseases using CPPs, such as CPP-coupled botulinum toxin A for cervical dystonia, TAT–PSD-95 for ischemic stroke, and TAT–JNKI-1 for hearing loss. With the advent of cancer immunotherapy, immunomodulation has emerged as an important strategy for the treatment of various diseases. We review recent advances in clinical trials of cell-penetrating peptide (CPP) applications for immunotherapy and also discuss their challenges and opportunities for preclinical studies in various immune diseases. CPP conjugation to antigenic peptides or proteins can enable efficient antigen uptake and cross-presentation by antigen-presenting cells (APCs), which induce both humoral and cytotoxic responses. In addition, CPP-coupled immune modulators can enhance antitumor immunity or anti-inflammatory effects to regulate allergies and autoimmunity. Given their huge advantages in overcoming delivery barriers, CPP-based strategies for immunomodulation could extend drug optimization and advance immunotherapy in various human diseases. With the advent of cancer immunotherapy, immunomodulation has emerged as an important strategy for the treatment of various diseases. We review recent advances in clinical trials of cell-penetrating peptide (CPP) applications for immunotherapy and also discuss their challenges and opportunities for preclinical studies in various immune diseases. CPP conjugation to antigenic peptides or proteins can enable efficient antigen uptake and cross-presentation by antigen-presenting cells (APCs), which induce both humoral and cytotoxic responses. In addition, CPP-coupled immune modulators can enhance antitumor immunity or anti-inflammatory effects to regulate allergies and autoimmunity. Given their huge advantages in overcoming delivery barriers, CPP-based strategies for immunomodulation could extend drug optimization and advance immunotherapy in various human diseases. peptides rich in positively charged amino acids that can interact with negatively charged membrane molecules and assist with endocytosis-mediated internalization. T cells that kill target cells via cytotoxic molecules such as perforin and granzyme B. induces memory T cells by inducing DCs to present the antigen to the T cells by delivering the antigen and the cell-penetrating peptide (CPP) conjugate. protein oligomers and innate immune system sensors that promote the activation of caspase-1 and inflammation. derived from common lymphoid progenitors, ILCs are activated by cytokines, do not require T cell receptor signaling, and play roles in mucosal immunity and immune homeostasis. a nanoparticle composed of one phospholipid layer that delivers siRNA or mRNA into cells. a component protein of chicken egg white that is used to induce antigen-specific T cell immune responses in mice. the study of the absorption, distribution, metabolism, and excretion of drugs in organisms to determine their effects. non-coding RNAs of 20–24 nt that interfere with the expression of a specific gene. receptors that are mainly expressed in innate immune cells such as macrophage and dendritic cells. TLRs recognize conserved molecules in pathogens and activate the immune response against the pathogens. a protein sequence derived from HIV-1 that has a protein transduction domain and is used as a CPP.