Biotherapy

Biotherapy - Clinical Bioenergy Treatment is a method of "bioenergy healing" where therapists are using hand movements with patterns of muscular tension and relaxation of the palm to induce changes in the patient's tissue or organs to promote healing via immune response due to homeostatic alteration. This pilot research is oriented towards the understanding of the biophysical changes during and after the bioenergy manual manipulation or due to biotherapy procedures. Observation is conducted in 2 different cases with therapy in person and at distance. The biophysical influence is measured by the digital infrared thermal camera before, during and after the therapy.

Like a tsunami, the SARS-Cov2 pandemic suddenly changed our programs and perspectives. Because traditional meetings are not allowed in the COVID era, the XVIII international meeting of the Italian Network for Tumor Biotherapy (NIBIT) went virtual on October 15–16, 2020. COVID-19 has been a formidable challenge for oncologists and immunologists. Thus, while maintaining the focus on cancer immunology and immunotherapy, most of the sessions also investigated how COVID-19 impacted these topics. Accordingly, “Coronavirus disease-19 (COVID-19) at the intersection between cancer, immunity and immunotherapy” was chosen as theme of the meeting. Plenary sessions were organized in two consecutive afternoons, in the intent to allow convenient time in the morning for usual business. Three poster sessions in the morning also allowed 20 investigators to orally present their most recent and exciting findings. With appreciation of almost 150 attendees, we at NIBIT were very pleased to meet the educational needs of its members and of young investigators committed to cancer immunotherapy.

Low dose oral interferon alpha has been shown to be of benefit in viral disease in animals. In a double-blind, placebo-controlled trial, 177 patients seropositive for HIV-1 were randomly assigned to receive placebo or recombinant human interferon alpha 2a (rIFN alpha). Endpoints were survival, alteration of disease classification, performance, and changes in CD4+ T cell numbers. There was a trend for improved survival in the group receiving rIFN alpha at the dose of 1.0 IU/lb. The changes in disease classification or in weight were not significantly different. Performance was improved to a greater extent (p=0.1) in the patients who received the two higher rIFN alpha dosages (1.0 IU/lb and 10.0 IU/lb) at 6 months. In addition, the CD4+ T cell count was improved only in the 1.0 IU/lb dose treatment group at 6 months. Treatment with low dose oral interferon at 1.0 IU/lb was associated with improved CD4+ T cell count, performance and a trend toward enhanced survival in HIV seropositive ...

The pleiotropic activities of IL-1 have fostered a series of studies on the structure-function relationship in these proteins. In fact, the attempt to dissociate different biological functions of IL-1 should simplify its therapeutic use. About human IL-1 beta, which has been more extensively studied in this respect, enzymatic cleavage of the precursor protein to generate the mature polypeptide appears necessary for its full biological activity. The almost complete integrity of the mature IL-1 beta protein is also required for its ability to bind to the receptor and trigger cellular functions. However, by the use of monoclonal antibodies and recombinant or synthetic peptides, it has been possible to map some IL-1 beta regions important for different activities. Both N-terminal and C-terminal fragments are important for receptor binding. A domain around amino acids 187-204 is apparently involved in the hyperalgesic effects of IL-1 beta. Finally, the fragment in position 163-171 appear...

Immunotherapy has been developed for the treatment of metastatic cancers refractory to conventional therapies. Immunotherapy utilizes immune cells and/or biological response modifiers (BRMs) to induce an anti-tumor response mediated by the patient's immune system. BRMs, including lymphokines and cytokines, are used as single agents or in combination for cancer therapy. Some BRMs, particularly interleukin 2 (IL-2), can activate and expand in vitro lymphocytes with anti-tumor reactivity which will be adoptively transferred to the patient. To enhance the therapeutic effect of immunotherapy, gene therapy is currently under investigation and involves the insertion of cytokine genes in immune cells or in tumor cells. The development and future of cancer immunotherapy will be discussed in this review.

Nanoparticles represent particularly attractive delivery systems for small interfering RNA (siRNA) and may provide the foundation for rational design and formulation of RNAi-triggering nanomedicines. siRNA can be delivered with a therapeutic intent using lipid-based delivery platforms such as stable nucleic acid lipid particles (SNALP) with a lipid bilayer containing cationic as well as fusogenic lipids and a diffusible PEG-lipid coat, polymers, cationic complexes, recombinant fusion proteins, conjugates, or polyconjugates. Several investigators have reported preclinical or early clinical proof of concept studies demonstrating that systemic delivery of siRNA nanoparticles targeting specific gene transcripts can elicit biologic responses. Therapeutic nanoparticles containing siRNA targeting specific genes that contribute to the aggressiveness and/or radiochemotherapy resistance of cancer cells may facilitate a paradigm shift in modern cancer therapy.

Dialysable leucocyte extract (DLE), obtained from lysed leucocytes, provide clinical effectiveness in a broad spectrum of diseases. Tumour necrosis factor (TNF) is raised in AIDS patients leading to an increase in human immunodeficiency virus (HIV) replication in vitro [1,2], whereas progression to AIDS in asymptomatic HIV infected individuals is retarded under treatment with DLE. In the present study we tested the DLE effect in vitro on both TNF biological activity (cytotoxicity) in L929 cells and its induction by lipopolysaccharide (LPS) in human monocytes as well as in whole blood from healthy donors. When monocytic cells were simultaneously exposed to LPS and DLE during a period of 5 1/2 hours, the induction of TNF was strongly diminished. The same inhibitory effect of DLE on TNF induction was observed when LPS was added to the culture medium prior to DLE. No significant effect of DLE on TNF-mediated cytotoxicity, even in the presence of the highest concentrations of DLE tested,...

We have demonstrated that in vitro preincubation with IL-1 or TNFa for 20 hours can protect human hematopoietic progenitors from lethal doses of 4-HC. On the other hand, preincubation with IL-6 or IL-3, in a similar fashion, did not provide any protection but in fact demonstrated a slight increase in 4-HC toxicity in the same experiments. The observation that IL-1 was still protective even when a purified cell population depleted of accessory cells was used is suggestive of a direct effect of IL-1. Our data also suggest that early progenitor cells including the replatable B;-CFC are the main target of that protection. We believe that using this in vitro assay system will enable us to investigate the possible mechanisms responsible for the protection of these primitive progenitors. From a clinical perspective, future studies should attempt to clarify whether protection by IL-1 is selective for normal hematopoietic cells versus malignant cells and whether these protected primitive pro...

We investigated possible mechanisms leading to the inhibition of the immune system in people with chronic disorders. Tumor cell produce protein released into the circulation, such as tumor associated antigens, may play an important role in processes preceding paralysis of the immune system. To test this hypothesis the following tumor associated antigens were used: AFP, OFP, CA-125, CA-50 and CA-19-9. Their role was assessed by modulating cytokine production in cord blood lymphocytes and peripheral white blood cells obtained from grown population of patients treated with colostrinin, an cytokine inducer. PHA, LPS and colostrinin were used as positive control in those essays. Each antigen tested individually induced IFN, TNF alpha and IL-6 in dose dependent fashion. None of the tested cytokines were spontaneously released by the cells. Data generated from these experiments indicated that tumor associated antigens are inducing type 1 cytokines in similar fashion as LPS or colostrinin. ...

Focused preclinical studies have been used to gain insight into the mechanism of therapeutic activity of cytokines, growth factors and biological response modifiers (BRMs). These data can then be used to develop a clinical hypothesis to facilitate the development of these new biological drugs. In this manuscript, we discuss a number of preclinical and clinical studies using interferon-gamma, IL-2, and the colony stimulating factors. The importance of the systematic profiling of the biological activity of such biological drugs is emphasized and we discuss the utility of the mechanistic data in their clinical development. The overall preclinical approach identifies the cellular, biochemical or gene regulatory event that is associated with the therapeutic activity of a biologic and this surrogate (be it biological, chemical, or quality of life) is then used to optimize the clinical protocol in a phase 1b trial. This, in theory, results in the rapid identification of the optimal dose, s...

To evaluate the advantage with regard to toxicity, response rate, time to progression and survival of combination chemoimmunotherapy over single-agent chemotherapy in patients with metastatic colorectal carcinoma (CRC), 30 patients were randomized to receive a combination of 5-fluorouracil (5-FU) by continuous i.v. infusion and plasma perfusion (PP) over protein A-Sepharose (group A), or a combination of 5-FU and PP over sepharose (group B) or 5-FU alone (group C). 5-FU was given at 1,000 mg/m2/d on days 1-5 of a 4-weekly cycle until progression. Patients of groups A and B received bi-weekly on-line PPs until disease progression or for a maximum of 19 treatments. PP was well tolerated and no severe or life-threatening toxicity was observed. The response rates were 10% for the group A (1 PR), 0% for the group B and 20% for the group C (1 CR + 1 PR). The times to tumor progression for patients in groups A and C were 22 months, 12 and 11 months, respectively and the median survival tim...

High level infant mortality rates and onset of drug resistance has led into the possible development of indigenous probiotics as alternative bacteriotherapy in the control of infantile bacterial diarrhoea. This study was to determine the in vitro inhibitory potential of four probiotic candidates obtained from Nigeria indigenous fermented foods and beverages and from faecal specimens of healthy infants on infantile Gram-positive diarrhoeagenic bacterial pathogens. Potential probiotic candidates, L. acidophilus AAOOL4, L. reuteri AAOOCH1, L. plantarum AAOO25NN and L. delbrueckii AAOOT20 were assayed for in vitro bactericidal effects on diarrhogenic bacteria test strains, Bacillus cereus 25S, B. cereus 32S, B. licheniformis 26S and B. licheniformis 39S. All the test strains inoculated into industrial infant weaning food already seeded with the probiotic strains were significantly inhibited within 96 hours L. acidophilus AAOOL4, L. reuteri AAOOCH1, L. plantarum AAOO25NN and L. delbrueckii AAOOT20 had in vitro bactericidal effects on bacteria isolates implicated in infantile diarrhoea, indicating the probiotic potential of the candidates.