Therapeutic Vaccines Targeting Neoantigens to Induce T-Cell Immunity against Cancers

Cancer immunotherapy has achieved multiple clinical benefits and has become an indispensable component of cancer treatment. Targeting tumor-specific antigens, also known as neoantigens, plays a crucial role in cancer immunotherapy. T cells of adaptive immunity that recognize neoantigens, but do not induce unwanted off-target effects, have demonstrated high efficacy and low side effects in cancer immunotherapy. Tumor neoantigens derived from accumulated genetic instability can be characterized using emerging technologies, such as high-throughput sequencing, bioinformatics, predictive algorithms, mass-spectrometry analyses, and immunogenicity validation. Neoepitopes with a higher affinity for major histocompatibility complexes can be identified and further applied to the field of cancer vaccines. Therapeutic vaccines composed of tumor lysates or cells and DNA, mRNA, or peptides of neoantigens have revoked adaptive immunity to kill cancer cells in clinical trials. Broad clinical applicability of these therapeutic cancer vaccines has emerged. In this review, we discuss recent progress in neoantigen identification and applications for cancer vaccines and the results of ongoing trials

Therapeutic Vaccines Targeting Neoantigens to Induce T-Cell Immunity against Cancers

Cancer immunotherapy has achieved multiple clinical benefits and has become an indispensable component of cancer treatment. Targeting tumor-specific antigens, also known as neoantigens, plays a crucial role in cancer immunotherapy. T cells of adaptive immunity that recognize neoantigens, but do not induce unwanted off-target effects, have demonstrated high efficacy and low side effects in cancer immunotherapy. Tumor neoantigens derived from accumulated genetic instability can be characterized using emerging technologies, such as high-throughput sequencing, bioinformatics, predictive algorithms, mass-spectrometry analyses, and immunogenicity validation. Neoepitopes with a higher affinity for major histocompatibility complexes can be identified and further applied to the field of cancer vaccines. Therapeutic vaccines composed of tumor lysates or cells and DNA, mRNA, or peptides of neoantigens have revoked adaptive immunity to kill cancer cells in clinical trials. Broad clinical applicability of these therapeutic cancer vaccines has emerged. In this review, we discuss recent progress in neoantigen identification and applications for cancer vaccines and the results of ongoing trials

Delayed Drug Hypersensitivity Reactions: Molecular Recognition, Genetic Susceptibility, and Immune Mediators

Drug hypersensitivity reactions are classified into immediate and delayed types, according to the onset time. In contrast to the immediate type, delayed drug hypersensitivity mainly involves T lymphocyte recognition of the drug antigens and cell activation. The clinical presentations of such hypersensitivity are various and range from mild reactions (e.g., maculopapular exanthema (MPE) and fixed drug eruption (FDE)), to drug-induced liver injury (DILI) and severe cutaneous adverse reactions (SCARs) (e.g., Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP)). The common culprits of delayed drug hypersensitivity include anti-epileptics, antibiotics, anti-gout agents, anti-viral drugs, etc. Delayed drug hypersensitivity is proposed to be initiated by different models of molecular recognition, composed of drug/metabolite antigen and endogenous peptide, HLA presentation, and T cell receptor (TCR) interaction. Increasing the genetic variants of HLA loci and drug metabolic enzymes has been identified to be responsible for delayed drug hypersensitivity. Furthermore, preferential TCR clonotypes, and the activation of cytotoxic proteins/cytokines/chemokines, are also involved in the pathogenesis of delayed drug hypersensitivity. This review provides a summary of the current understanding of the molecular recognition, genetic susceptibility, and immune mediators of delayed drug hypersensitivity

Recent Development and Clinical Application of Cancer Vaccine: Targeting Neoantigens

Recently, increasing data show that immunotherapy could be a powerful weapon against cancers. Comparing to the traditional surgery, chemotherapy or radiotherapy, immunotherapy more specifically targets cancer cells, giving rise to the opportunities to the patients to have higher response rates and better quality of life and even to cure the disease. Cancer vaccines could be designed to target tumor-associated antigens (TAAs), cancer germline antigens, virus-associated antigens, or tumor-specific antigens (TSAs), which are also called neoantigens. The cancer vaccines could be cell-based (e.g., dendritic cell vaccine provenge (sipuleucel-T) targeting prostatic acid phosphatase for metastatic prostate cancer), peptide/protein-based, or gene- (DNA/RNA) based, with the different kinds of adjuvants. Neoantigens are tumor-specific and could be presented by MHC molecules and recognized by T lymphocytes, serving the ideal immune targets to increase the therapeutic specificity and decrease the risk of nonspecific autoimmunity. By targeting the shared antigens and private epitopes, the cancer vaccine has potential to treat the disease. Accordingly, personalized neoantigen-based immunotherapies are emerging. In this article, we review the literature and evidence of the advantage and application of cancer vaccine. We summarize the recent clinical trials of neoantigen cancer vaccines which were designed according to the patients’ personal mutanome. With the rapid development of personalized immunotherapy, it is believed that tumors could be efficiently controlled and become curable in the new era of precision medicine

Fabrication of Polymer Nanopeapods in the Nanopores of Anodic Aluminum Oxide Templates Using a Double-Solution Wetting Method

Although one-dimensional polymer nanomaterials can be prepared by approaches such as the template method, the control over the morphologies of one-dimensional polymer nanomaterials containing multiple components is still a great challenge. In this work, we investigate the formation of polymer nanopeapods using a novel double-solution wetting method in the nanopores of anodic aluminum oxide (AAO) templates. A polystyrene (PS) solution in dimethylformamide (DMF) is first introduced into the nanopores of the AAO templates. Then a second polymer solution of poly­(methyl methacrylate) (PMMA) in acetic acid is infiltrated into the nanopores. Because of the stronger interaction between acetic acid and aluminum oxide than that between DMF and aluminum oxide, the PMMA solution preferentially wets the pore walls of the templates and the PS solution is isolated in the center of the nanopores. After the evaporation of the solvent, peapod-like PS/PMMA nanostructures are obtained, where the shell and the core are composed of PMMA and PS, respectively. The compositions of the polymer nanopeapods are confirmed by removing PS or PMMA selectively. The formation mechanism of the nanostructures is related to the Rayleigh-instability-type transformation and further studied by changing experimental parameters such as the polymer concentration or the polymer molecular weight. This work not only provides a simple approach to prepare multicomponent polymer nanomaterials with controlled morphologies and sizes, but also contributes to a deeper understanding of polymer–solvent interactions in confined geometries

Biogas production from most agricultural organic wastes by anaerobic digestion in Taiwan

Agricultural organic wastes (AOW) have the potential to provide bioenergy particularly found in biogas by anaerobic digestion (AD). In this study, the biogas production (BP) of AOW was obtained by batch AD with anaerobic digesters (500 mL) at 35°C incubator. The results showed that BP values in terms of volatile solids (VS) from rice husk, rice straw, flower residues, fruit and vegetable residues, wasted oyster shell residue (WOSR), fishery residues, livestock and poultry manures, livestock and poultry slaughter wastes (LPSW), and eight equally mixed wastes (EEMW) were 84.03, 193.36, 153.32, 76.27, 150.48, 63.26, 169.63, 615.74, and 172.83 mL/g VS, respectively. LPSW showed the highest μ m of 16.99 mL/g VS-d, the highest BP of 615.74 mL/g VS and the highest bioconversion efficiency of 65.98% compared to the other organic wastes. BP from the most AOW in Taiwan by AD was estimated to be 768,567,753 (743,522,223, excluding WOSR) m 3 /year. The annual BP of 768,567,753 m 3 /year of the eight total major AOW by AD was lower (∼20.11%) than 961,989,781 m 3 /year of the EEMW by anaerobic co-digestion. Result also showed that modified Gompertz equation was suitable to describe BP accumulation and BP rate. </p