• HV
• HV-LV
• MT: Delivery Strategies
• cancer immunology
• cell damage
• colorectal cancer
• electric pulses
• electroporation
• gene electrotransfer
• mouse tumor model

• Cancer immunotherapy
• DNA vaccine
• Peptide vaccine
• Telomerase
• hTERT

• antitumor immune response
• calcium phosphate (CaP)
• nanoparticle vaccine
• review
• tumor microenvironment

• YJS20210324 Scientific Research Project of Education Department of Anhui Province
• 81972829 National Natural Science Foundation of China
• 2022ZLA006 Research and Development of Intelligent Surgical Navigation and Operating System for Precise Liver Resection
• 10001020507 Start-up Fund for Talent Researchers of Tsinghua University

• COVID-19
• Cancer vaccine
• Infectious disease
• Nucleic acid vaccine

• Vaccines, DNA/administration & dosage
• Vaccines, DNA/immunology
• Humans
• COVID-19 Vaccines/administration & dosage
• COVID-19 Vaccines/immunology
• mRNA Vaccines
• COVID-19/prevention & control
• SARS-CoV-2/immunology
• SARS-CoV-2/genetics
• Animals

• R35 GM145362 NIGMS NIH HHS

• alternative lengthening of telomeres (ALT)
• cancer therapy
• telomerase
• telomere dynamics

• Humans
• Neoplasms/drug therapy
• Neoplasms/therapy
• Telomere/drug effects
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/chemistry
• Telomerase/antagonists & inhibitors
• Animals
• Drug Delivery Systems/methods
• Nanoparticles/chemistry
• Immunotherapy/methods
• Neoplastic Stem Cells/drug effects

• Clinical trials
• Colorectal cancer
• DNA mismatch repair
• Immune checkpoint inhibitors
• Immunotherapy
• Microsatellite instability
• Microsatellite stability

• Humans
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/immunology
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/genetics
• Immune Checkpoint Inhibitors/therapeutic use
• Immune Checkpoint Inhibitors/adverse effects
• Clinical Trials as Topic
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Programmed Cell Death 1 Receptor/immunology
• Immunotherapy/methods
• CTLA-4 Antigen/antagonists & inhibitors
• CTLA-4 Antigen/immunology
• Treatment Outcome
• B7-H1 Antigen/antagonists & inhibitors
• B7-H1 Antigen/immunology

• biomarkers
• castration-resistant prostate cancer
• dendritic cell-based vaccines
• immunotherapy
• prostate cancer
• tumor microenvironment

• RNA sequencing
• plasmid electroporation
• signaling pathways
• skeletal muscle

• R01 CA196796 NCI NIH HHS

• breast cancer
• resistance
• telomerase
• therapy

• Female
• Humans
• Telomerase/metabolism
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Telomere/metabolism
• Immunotherapy
• Neoplasms/pathology
• Enzyme Inhibitors/therapeutic use

• DNA vaccine
• SARS-CoV-2
• animal models
• antiviral immunity
• protection

• Animals
• Antibodies, Neutralizing/immunology
• Antibodies, Viral/immunology
• COVID-19/genetics
• COVID-19/prevention & control
• COVID-19/virology
• COVID-19 Vaccines/administration & dosage
• Female
• Ferrets
• Humans
• Immunization/methods
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Transgenic
• Models, Animal
• Protein Domains
• Rats, Sprague-Dawley
• SARS-CoV-2/isolation & purification
• Spike Glycoprotein, Coronavirus/immunology
• Vaccines, DNA/administration & dosage
• Rats

Telomeres cap the ends of eukaryotic chromosomes and are indispensable chromatin structures for genome protection and replication. Telomere length maintenance has been attributed to several functional modulators, including telomerase, the shelterin complex, and the CST complex, synergizing with DNA replication, repair, and the RNA metabolism pathway components. As dysfunctional telomere maintenance and telomerase activation are associated with several human diseases, including cancer, the molecular mechanisms behind telomere length regulation and protection need particular emphasis. Cancer cells exhibit telomerase activation, enabling replicative immortality. Telomerase reverse transcriptase (TERT) activation is involved in cancer development through diverse activities other than mediating telomere elongation. This review describes the telomere functions, the role of functional modulators, the implications in cancer development, and the future therapeutic opportunities.

Adenovirus vectors are the most frequently used agents for gene therapy, including oncolytic therapy and vaccine development. It’s hard to overestimate the value of adenoviruses during the COVID-19 pandemic as to date four out of four approved viral vector-based SARS-CoV-2 vaccines are developed on adenovirus platform. The vast majority of adenoviral vectors are based on the most studied human adenovirus type 5 (HAdV-C5), however, its immunogenicity often hampers the clinical translation of HAdV-C5 vectors. The search of less seroprevalent adenovirus types led to another species C adenovirus, Adenovirus type 6 (HAdV-C6). HAdV-C6 possesses high oncolytic efficacy against multiple cancer types and remarkable ability to induce the immune response towards carrying antigens. Being genetically very close to HAdV-C5, HAdV-C6 differs from HAdV-C5 in structure of the most abundant capsid protein, hexon. This leads to the ability of HAdV-C6 to evade the uptake by Kupffer cells as well as to distinct opsonization by immunoglobulins and other blood proteins, influencing the overall biodistribution of HAdV-C6 after systemic administration. This review describes the structural features of HAdV-C6, its interaction with liver cells and blood factors, summarizes the previous experiences using HAdV-C6, and provides the rationale behind the use of HAdV-C6 for vaccine and anticancer drugs developments.

• Ad5
• Ad6
• Kupffer cells
• adenovirus
• immunotherapy
• liver tropism
• oncolytic viruses
• serotype 6
• vaccine
• virotherapy

Electrochemotherapy (ECT) is an effective bioelectrochemical procedure that uses controlled electrical pulses to facilitate the increase of intracellular concentration of certain substances (electropermeabilization/ reversible electroporation). ECT using antitumor drugs such as bleomycin and cisplatin is a minimally invasive targeted therapy that can be used as an alternative for oncologic patients not eligible for surgery or other standard therapies. Even though ECT is mainly applied as palliative care for metastases, it may also be used for primary tumors that are unresectable due to size and location. Skin neoplasms are the main clinical indication of ECT, the procedure reporting good curative results and high efficiency across all tumor types, including melanoma. In daily practice, there are many cases in which the patient’s quality of life can be significantly improved by a safe procedure such as ECT. Its popularity must be increased because it has a safe profile and minor local adverse reactions. The method can be used by dermatologists, oncologists, and surgeons. The aim of this paper is to review recent literature concerning electrochemotherapy and other clinical applications of electroporation for the targeted therapy of metastatic melanoma.

• advanced melanoma
• electrochemotherapy
• electropermeabilization
• electroporation
• gene transfer
• metastatic melanoma
• targeted therapy

Human telomerase reverse transcriptase (hTERT) is frequently classified as a ‘universal’ tumor associated antigen due to its expression in a vast number of cancers. We evaluated plasmid DNA-encoded hTERT as an immunotherapy across nine cancer types.

A phase 1 clinical trial was conducted in adult patients with no evidence of disease following definitive surgery and standard therapy, who were at high risk of relapse. Plasmid DNA encoding one of two hTERT variants (INO-1400 or INO-1401) with or without plasmid DNA encoding interleukin 12 (IL-12) (INO-9012) was delivered intramuscularly concurrent with the application of the CELLECTRA constant-current electroporation device 4 times across 12 weeks. Safety assessments and immune monitoring against native (germline, non-mutated, non-plasmid matched) hTERT antigen were performed. The largest cohort of patients enrolled had pancreatic cancer, allowing for additional targeted assessments for this tumor type.

Of the 93 enrolled patients who received at least one dose, 88 had at least one adverse event; the majority were grade 1 or 2, related to injection site. At 18 months, 54.8% (51/93) patients were disease-free, with median disease-free survival (DFS) not reached by end of study. For patients with pancreatic cancer, the median DFS was 9 months, with 41.4% of these patients remaining disease-free at 18 months. hTERT immunotherapy induced a de novo cellular immune response or enhanced pre-existing cellular responses to native hTERT in 96% (88/92) of patients with various cancer types. Treatment with INO-1400/INO-1401±INO-9012 drove hTERT-specific IFN-γ production, generated hTERT-specific CD4+ and CD8+ T cells expressing the activation marker CD38, and induced hTERT-specific activated CD8 +CTLs as defined by cells expressing perforin and granzymes. The addition of plasmid IL-12 adjuvant elicited higher magnitudes of cellular responses including IFN-γ production, activated CD4+ and CD8+ T cells, and activated CD8+CTLs. In a subset analysis of pancreatic cancer patients, the presence of immunotherapy-induced activated CD8+ T cells expressing PD-1, granzymes and perforin correlated with survival.

Plasmid DNA-encoded hTERT/IL-12 DNA immunotherapy was well-tolerated, immune responses were noted across all tumor types, and a specific CD8+ phenotype increased by the immunotherapy was significantly correlated with survival in patients with pancreatic cancer.

• cellular
• immunity
• immunotherapy

• cancer vaccination
• cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
• early stage
• immune checkpoint inhibitor
• immunotherapy
• non-small cell lung cancer (NSCLC)
• programmed death-ligand 1 (PD-L1)
• surgery

• 109-2628-B-182A-009 Ministry of Science and Technology, Taiwan
• CMRPG3K1561 Chang Gung Memorial Hospital, Linkou
• CMRPG3K1151 Chang Gung Memorial Hospital, Linkou

Therapeutic vaccination regimens inducing clinically effective tumor-specific CD8⁺ T lymphocyte (CTL) responses are an unmet medical need. We engineer two distantly related arenaviruses, Pichinde virus and lymphocytic choriomeningitis virus, for therapeutic cancer vaccination. In mice, life-replicating vector formats of these two viruses delivering a self-antigen in a heterologous prime-boost regimen induce tumor-specific CTL responses up to 50% of the circulating CD8 T cell pool. This CTL attack eliminates established solid tumors in a significant proportion of animals, accompanied by protection against tumor rechallenge. The magnitude of CTL responses is alarmin driven and requires combining two genealogically distantly related arenaviruses. Vector-neutralizing antibodies do not inhibit booster immunizations by the same vector or by closely related vectors. Rather, CTL immunodominance hierarchies favor vector backbone-targeted responses at the expense of self-reactive CTLs. These findings establish an arenavirus-based immunotherapy regimen that allows reshuffling of immunodominance hierarchies and breaking self-directed tolerance for efficient tumor control.

Engineered arenaviruses induce potent tumor self-specific CD8 T cell (CTL) response

• CD8 T cells
• Pichinde virus
• anti-vector immunity
• arenavirus
• lymphocytic choriomeningitis virus
• pre-existing immunity
• therapeutic tumor vaccine
• tumor control
• viral genealogy

• CD4+ and CD8+ lytic T cell response
• antibodies
• electroporation
• epitopes
• intradermal DNA immunization
• lentiviral transduction
• metastasis
• murine adenocarcinoma cells
• rejection
• reverse transcriptase domain
• suppression
• telomerase reverse transcriptase (TERT)
• therapeutic cancer vaccines
• tumor growth

• LZP-2018/2-0308 Latvijas Zinātnes Padome
• 17_54_30002 Russian Foundation for Basic Research
• 17-00-00085 Russian Foundation for Basic Research
• 17_04_00583 Russian Foundation for Basic Research
• CA17140 NANO2CLINIC COST actions
• CA16231 ENOVA COST actions
• EAVI 681137 H2020 project

Virus-like particles (VLP) spontaneously assemble from viral structural proteins. They are naturally biocompatible and non-infectious. VLP can serve as a platform for many potential vaccine epitopes, display them in a dense repeating array, and elicit antibodies against non-immunogenic substances, including tumor-associated self-antigens. Genetic or chemical conjugation facilitates the multivalent display of a homologous or heterologous epitope. Most VLP range in diameter from 25 to 100 nm and, in most cases, drain freely into the lymphatic vessels and induce antibodies with high titers and affinity without the need for additional adjuvants. VLP administration can be performed using different strategies, regimens, and doses to improve the immunogenicity of the antigen they expose on their surface. This article summarizes the features of VLP and presents them as a relevant platform technology to address not only infectious diseases but also chronic diseases and cancer.

• cancer
• immunotherapy
• vaccine
• virus-like particles