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Tumor therapy with replication competent viruses is an exciting approach to cancer eradication where viruses are engineered to specifically infect, replicate, spread and kill tumor cells. The outcome of tumor virotherapy is complex due to the variable interactions between the cancer cell and virus populations as well as the immune response. Oncolytic viruses are highly efficient in killing tumor cells in vitro, especially in a 2D monolayer of tumor cells, their efficiency is significantly lower in a 3D environment, both in vitro and in vivo. This indicates that the spatial dimension may have a major influence on the dynamics of virus spread. We study the dynamic behavior of a spatially explicit computational model of tumor and virus interactions using a combination of in vitro 2D and 3D experimental studies to inform the models. We determine the number of nearest neighbor tumor cells in 2D (median = 6) and 3D tumor spheroids (median = 16) and how this influences virus spread and the outcome of therapy. The parameter range leading to tumor eradication is small and even harder to achieve in 3D. The lower efficiency in 3D exists despite the presence of many more adjacent cells in the 3D environment that results in a shorter time to reach equilibrium. The mean field mathematical models generally used to describe tumor virotherapy appear to provide an overoptimistic view of the outcomes of therapy. Three dimensional space provides a significant barrier to efficient and complete virus spread within tumors and needs to be explicitly taken into account for virus optimization to achieve the desired outcome of therapy. [ABSTRACT FROM AUTHOR]

Background: Interstitial brachytherapy for localised prostate cancer may be followed by transient increases in prostate-specific antigen (PSA) that resolve without therapy. Such PSA bounces may be associated with an improved outcome but often cause alarm in the patient and physician, and have defied explanation.Methods: We developed a mathematical model to capture the interactions between the tumour, radiation and anti-tumour immune response. The model was fitted to data from a large cohort of patients treated exclusively with interstitial brachytherapy. Immunohistological analysis for T-cell infiltration within the same tumours was also performed.Results: Our minimal model captures well the dynamics of the tumour after therapy, and suggests that a strong anti-tumour immune response coupled with the therapeutic effect of radiation on the tumour is responsible for the PSA bounce. Patients who experience a PSA bounce had a higher density of CD3 and CD8 cells within the tumour that likely contribute to the PSA bounce and the overall better outcomes observed.Conclusions: Our observations provide a novel and unifying explanation for the PSA bounce in patients with early prostate cancer and also have implications for the use of immune-based therapies in such patients to improve outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Estimates of T regulatory cell populations in the periphery of patients with Crohn’s disease are confounded by disease activity and concomitant immunotherapeutic agents known to affect T cell proliferation and survival. We performed deuterium pulse/chase experiments in patients with quiescent Crohn’s disease on no immunotherapy and healthy control subjects to estimate T regulatory cell kinetics. Quantification of deuterated DNA isolated from T cell subsets over 10days was determined by mass spectrophotometry. We demonstrate enhanced proliferation within the T regulatory cell population from patients with Crohn’s disease when compared to non-T regulatory cells and T regulatory cells from healthy control subjects. We speculate that T regulatory cells isolated from the periphery of patients with Crohn’s disease experience persistent antigen stimulation resulting in excess proliferative rates. [Copyright &y& Elsevier]