Search

Simple Summary: Although many new cancer drugs look like they are working in the laboratory, they fail when tested on real people. This is often because the cancer cell models they are tested on are short-term, but cancer grows in people over a longer period, and things change over time. This is not a criticism of cancer laboratories, but more a realism of the limits of scientific research. This is why we developed this longer-lasting model of colorectal cancer that has moved around the body. At the same time, we used this model to test next-generation delivery of chemotherapy drugs to tumors with an advanced targeting virus. All levels of cancer research have value, both short-term and long-term, but the longer strategies need to catch up, so this study demonstrates what can be achieved with 3D bioprinting tumor models and testing viruses transformed for good. Long-term modelization of cancer as it changes in the human body is a difficult goal, particularly when designing and testing new therapeutic strategies. This becomes even more difficult with metastasis modeling to show chemotherapeutic molecule delivery directly to tumoral cells. Advanced therapeutics, including oncolytic viruses, antibody-based and cell-based therapies are increasing. The question is, are screening tests also evolving? Next-generation therapeutics need equally advanced screening tests, which whilst difficult to achieve, are the goal of our work here, creating models of micro- and macrotumors using 3D bioprinting. We developed advanced colorectal cancer tumor processing techniques to provide options for cellular expansion, microtumor printing, and long-term models, which allow for the evaluation of the kinetics of penetration testing, therapeutic success, targeted therapies, and personalized medicine. We describe how we tested tumors from a primary colorectal patient and, applying 3D bioprinting, matured long-term models for oncolytic metastatic screening. Three-dimensional microtumors were kept alive for the longest time ever recorded in vitro, allowing longitudinal studies, screening of oncolytic viruses and realistic modelization of colorectal cancer. These 3D bioprinted models were maintained for around 6 months and were able to demonstrate the effective delivery of a product to the tumoral environment and represent a step forward in therapeutic screening. [ABSTRACT FROM AUTHOR]

Abstract: Objective. – The feasibility of gene transfer to myocardial tissue using viral vectors was investigated over the last few years. In this study we report gene transfer using a recently described improved of Herpes simplex virus (HSV-1)-derived amplicon vectors and demonstrate that these vectors are a powerful and potentially very interesting tool for gene transfer into neonatal primary as well as in adult cardiac myocytes. Methods and results. – Non-pathogenic HSV-1 amplicon vectors simultaneously expressing GFP and LacZ were constructed using a novel helper system that yields essentially helper-free vector particles. These vectors were used to infect either cultured primary neonatal rat cardiomyocytes or adult cardiac tissue. Transgenic expression was quantified using a FACS (GFP) or X-gal staining (LacZ). Infection of primary cardiomyocytes showed efficient transduction even at very low multiplicity of infection (MOI), and expression increased with the infectious dose. By investigating release of lactate dehydrogenase (LDH) or spontaneous beating of the cells, we failed to detect cytotoxic effects in cardiomyocytes infected at high MOI. Thin slices of adult cardiac tissue placed in medium containing vectors also showed very good levels of transduction, without any evidence of toxic effects. Conclusions. – Helper-free amplicon vectors very efficiently transduce genes into cardiomyocytes. Our results indicate similar or better transduction efficiencies than those reported using other vector systems. Furthermore, the very high transgenic capacity of amplicon vectors (up to 150 kbp) makes these vectors a unique and very suitable system to transduce large genomic sequences into cardiomyocytes. [Copyright &y& Elsevier]

[Display omitted] • Immunocompetent Cancer-on-Chips (iCoCs) can replicate complex tumor microenvironments. • iCoCs provide powerful tools for immuno-oncology research and immunotherapy testing. • Various iCoCs have been applied for mechanistic research and efficacy assessment. • Flexibility in design and readouts paves the way for further applications of iCoCs. The advances in cancer immunotherapy come with several obstacles, limiting its widespread use and benefits so far only to a small subset of patients. One of the underlying challenges remains to be the lack of representative nonclinical models that translate to human immunity and are able to predict clinical efficacy and safety outcomes. In recent years, immunocompetent Cancer-on-Chip models emerge as an alternative human-based platform that enables the integration and manipulation of complex tumor microenvironment. In this review, we discuss novel opportunities offered by Cancer-on-Chip models to advance (mechanistic) immuno-oncology research, ranging from design flexibility to multimodal analysis approaches. We then exemplify their (potential) applications for the research and development of adoptive cell therapy, immune checkpoint therapy, cytokine therapy, oncolytic virus, and cancer vaccines. [ABSTRACT FROM AUTHOR]

Organ-on-chip and tumor-on-chip microfluidic cell cultures represent a fast-growing research field for modelling organ functions and diseases, for drug development, and for promising applications in personalized medicine. Still, one of the bottlenecks of this technology is the analysis of the huge amount of bio-images acquired in these dynamic 3D microenvironments, a task that we propose to achieve by exploiting the interdisciplinary contributions of computer science and electronic engineering. In this work, we apply this strategy to the study of oncolytic vaccinia virus (OVV), an emerging agent in cancer immunotherapy. Infection and killing of cancer cells by OVV were recapitulated and directly imaged in tumor-on-chip. By developing and applying appropriate image analysis strategies and advanced automatic algorithms, we uncovered synergistic cooperation of OVV and immune cells to kill cancer cells. Moreover, we observed that the kinetics of immune cells were modified in presence of OVV and that these immune modulations varied during the course of infection. A correlation between cancer cell infection and cancer-immune interaction time was pointed out, strongly supporting a cause-effect relationship between infection of cancer cells and their recognition by the immune cells. These results shed new light on the mode of action of OVV, and suggest new clinical avenues for immunotherapy developments. • Infection and killing of cancer cells by oncolytic vaccinia virus (OVV) were recapitulated and directly imaged in tumor-on-chip • Conception and application of novel image analysis strategies and advanced automatic algorithms for tumor on-chip experiments boosted the discovery of original findings on OVV mode of action. • OVV require the cooperation of immune cells to efficiently kill cancer cells. • A meaningful correlation exists between OVV infection of cancer cells and immune-cancer cell interactions. [ABSTRACT FROM AUTHOR]

The article talks about Oncolytic Viruses (OV) which attack cancer cells and triggers anti tumor response in patients body. Research is being done on Vaccines for cancer which include T-vec which is used to stimulate immunity along with granulocyte-macrophage colony-stimulating factor and Cytotoxic T lymphocyte-associated molecule-4 which acts as inhibitors. Inhibitors are also developed for patients suffering from melanoma and Measles Virus.