Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution.

Oncolytic viruses and combinatorial immunotherapy for cancer (this Special Issue) are both part of cancer treatment at IOZK. This review focusses on an individual multimodal cancer immunotherapy concept developed by IOZK, Cologne, Germany. The scientific rationale for employing three main components is explained: (i) oncolytic Newcastle disease virus, (ii) modulated electrohyperthermia and (iii) individual tumor antigen and oncolytic virus modified dendritic cell vaccine (IO-VAC).

Methods behind oncolytic virus-based DC vaccines in cancer: Toward a multiphase combined treatment strategy for Glioblastoma (GBM) patients.

Glioblastoma (GBM) remains an orphan cancer disease with poor outcome. Novel treatment strategies are needed. Immunotherapy has several modes of action.

The Application of Evidence-Based Medicine in Individualized Medicine.

The fundamental aim of healthcare is to improve overall health of the population by providing state-of-the-art healthcare for individuals at an affordable cost. The foundation for this system is largely referred to as "evidence-based medicine". Too often, evidence-based medicine is based solely on so-called "best research evidence", collected through randomized controlled trials while disregarding clinical expertise and patient expectations.

Individualized Multimodal Immunotherapy for Adults with IDH1 Wild-Type GBM: A Single Institute Experience.

Synergistic activity between maintenance temozolomide (TMZm) and individualized multimodal immunotherapy (IMI) during/after first-line treatment has been suggested to improve the overall survival (OS) of adults with IDH1 wild-type MGMT promoter-unmethylated (unmeth) GBM. We expand the data and include the OS of MGMT promoter-methylated (meth) adults with GBM. Unmeth (10 f, 18 m) and meth (12 f, 10 m) patients treated between 27 May 2015 and 1 January 2022 were analyzed retrospectively.

Counteracting Immunosuppression in the Tumor Microenvironment by Oncolytic Newcastle Disease Virus and Cellular Immunotherapy.

An apparent paradox exists between the evidence for spontaneous systemic T cell- mediated anti-tumor immune responses in cancer patients, observed particularly in their bone marrow, and local tumor growth in the periphery. This phenomenon, known as "concomitant immunity" suggests that the local tumor and its tumor microenvironment (TME) prevent systemic antitumor immunity to become effective. Oncolytic Newcastle disease virus (NDV), an agent with inherent anti-neoplastic and immune stimulatory properties, is capable of breaking therapy resistance and immunosuppression.

Molecular Mechanisms of Anti-Neoplastic and Immune Stimulatory Properties of Oncolytic Newcastle Disease Virus.

Oncolytic viruses represent interesting anti-cancer agents with high tumor selectivity and immune stimulatory potential. The present review provides an update of the molecular mechanisms of the anti-neoplastic and immune stimulatory properties of the avian paramyxovirus, Newcastle Disease Virus (NDV). The anti-neoplastic activities of NDV include (i) the endocytic targeting of the GTPase Rac1 in Ras-transformed human tumorigenic cells; (ii) the switch from cellular protein to viral protein synthesis and the induction of autophagy mediated by viral nucleoprotein NP; (iii) the virus replication mediated by viral RNA polymerase (large protein (L), associated with phosphoprotein (P)); (iv) the facilitation of NDV spread in tumors via the membrane budding of the virus progeny with the help of matrix protein (M) and fusion protein (F); and (v) the oncolysis via apoptosis, necroptosis, pyroptosis, or ferroptosis associated with immunogenic cell death.

Synergy between TMZ and individualized multimodal immunotherapy to improve overall survival of IDH1 wild-type MGMT promoter-unmethylated GBM patients.

The prognosis of IDH1 wild-type MGMT promoter-unmethylated GBM patients remains poor. Addition of Temozolomide (TMZ) to first-line local treatment shifted the median overall survival (OS) from 11.8 to 12.

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications.

A dose-response relationship to stressors, according to the hormesis theory, is characterized by low-dose stimulation and high-dose inhibition. It is non-linear with a low-dose optimum. Stress responses by cells lead to adapted vitality and fitness.

Randomized Controlled Immunotherapy Clinical Trials for GBM Challenged.

Immunotherapies represent a promising strategy for glioblastoma multiforme (GBM) treatment. Different immunotherapies include the use of checkpoint inhibitors, adoptive cell therapies such as chimeric antigen receptor (CAR) T cells, and vaccines such as dendritic cell vaccines. Antibodies have also been used as toxin or radioactive particle delivery vehicles to eliminate target cells in the treatment of GBM.

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism.

Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria-156 brand new publications from 2019 and 2020-have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms.

Evidence-Based Medicine in Oncology: Commercial Versus Patient Benefit.

At times of personalized and individualized medicine the concept of randomized- controlled clinical trials (RCTs) is being questioned. This review article explains principles of evidence-based medicine in oncology and shows an example of how evidence can be generated independently from RCTs. Personalized medicine involves molecular analysis of tumor properties and targeted therapy with small molecule inhibitors.

Position paper: new insights into the immunobiology and dynamics of tumor-host interactions require adaptations of clinical studies.

Introduction: Prospective double-blind placebo-controlled randomized clinical trials (RCTs) are considered standard for the proof of the efficacy of oncologic therapies. Molecular methods have provided new insights into tumor biology and led to the development of targeted therapies. Due to the increasing complexity of molecular tumor characteristics and of the individuality of specific anti-tumor immune reactivity, RCTs are unfortunately only of limited use.

Addition of Multimodal Immunotherapy to Combination Treatment Strategies for Children with DIPG: A Single Institution Experience.

The prognosis of children with diffuse intrinsic pontine glioma (DIPG) remains dismal despite radio- and chemotherapy or molecular-targeted therapy. Immunotherapy is a powerful and promising approach for improving the overall survival (OS) of children with DIPG. A retrospective analysis for feasibility, immune responsiveness, and OS was performed on 41 children treated in compassionate use with multimodal therapy consisting of Newcastle disease virus, hyperthermia, and autologous dendritic cell vaccines as part of an individualized combinatorial treatment approach for DIPG patients.

Cancer Vaccines and Oncolytic Viruses Exert Profoundly Lower Side Effects in Cancer Patients than Other Systemic Therapies: A Comparative Analysis.

This review compares cytotoxic drugs, targeted therapies, and immunotherapies with regard to mechanisms and side effects. Targeted therapies relate to small molecule inhibitors. Immunotherapies include checkpoint inhibitory antibodies, chimeric antigen receptor (CAR) T-cells, cancer vaccines, and oncolytic viruses.

New Insights into Mechanisms of Long-term Protective Anti-tumor Immunity Induced by Cancer Vaccines Modified by Virus Infection.

The topic is how to achieve long-term protective anti-tumor immunity by anti-cancer vaccination and what are its mechanisms. Cancer vaccines should instruct the immune system regarding relevant cancer targets and contain signals for innate immunity activation. Of central importance is T-cell mediated immunity and thus a detailed understanding of cognate interactions between tumor antigen (TA)-specific T cells and TA-presenting dendritic cells.

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance.

From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review).

The side effects of systemic chemotherapy used to treat cancer are often severe. For decades, oncologists have focused on treating the tumor, which may result in damage to the tumor‑bearing host and its immune system. Recently, much attention has been paid to the immune system of patients and its activation via biological therapies.

Fifty Years of Clinical Application of Newcastle Disease Virus: Time to Celebrate!

This review provides an overview of 50 years of basic and clinical research on an oncolytic avian virus, Newcastle Disease Virus (NDV), which has particular anti-neoplastic and immune stimulatory properties. Of special interest is the fact that this biological agent induces immunogenic cell death and systemic anti-tumor immunity. Furthermore, localized oncolytic virotherapy with NDV was shown to overcome systemic tumor resistance to immune checkpoint blockade immunotherapy.

Immunobiology of Newcastle Disease Virus and Its Use for Prophylactic Vaccination in Poultry and as Adjuvant for Therapeutic Vaccination in Cancer Patients.

Newcastle disease (ND) is one of the most important diseases of poultry worldwide. In the last decades, molecular research has gained a lot of new information about its causative agent, (NDV). In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years.

Cancer-reactive memory T cells from bone marrow: Spontaneous induction and therapeutic potential (Review).

Cognate interactions between naïve tumor antigen (TA)-specific T cells and TA-presenting dendritic cells (DCs) are facilitated by secondary lymphoid organs such as lymph nodes or the spleen. These can result either in TA-specific tolerance or, depending on environmental costimulatory signals, in TA-specific immune responses. In the present review, we describe such events for the bone marrow (BM) when blood-borne TA, released from the primary tumor or expressed by blood circulating tumor cells or DCs enters the BM stroma and parenchyma.

Oncolytic Newcastle disease virus as a prospective anti-cancer therapy. A biologic agent with potential to break therapy resistance.

Introduction: Oncolytic viruses (OVs) selectively replicate in tumor cells and cause cancer cell death. Most OVs in clinical studies are genetically engineered. In contrast, the avian Newcastle disease virus (NDV) is a naturally oncolytic RNA virus.

Long-term survival of a breast cancer patient with extensive liver metastases upon immune and virotherapy: a case report.

Liver metastases in breast cancer are associated with a poor prognosis. We report long-term survival of a patient with breast cancer and liver metastases. After operation the patient declined further standard therapy.

Signaling through RIG-I and type I interferon receptor: Immune activation by Newcastle disease virus in man versus immune evasion by Ebola virus (Review).

In this review, two types of RNA viruses are compared with regard to the type I interferon (IFN) response in order to obtain a better understanding of the molecular mechanisms of immune activation or evasion. Upon human infection, both viruses exert either beneficial or detrimental effects. The Newcastle disease virus (NDV), is a type strain for avian paramyxoviruses, while the Ebola virus (EBOV), is a virus affecting primates.