TUMOR-IMMUNE SYSTEM INTERACTION: MODELING THE TUMOR-STIMULATED PROLIFERATION OF EFFECTORS AND IMMUNOTHERAPY

2006 ◽  
Vol 16 (08) ◽  
pp. 1375-1401 ◽  
Author(s):  
A. D'ONOFRIO
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Local Stability ◽  
Tumor Burden ◽  
Stable Limit ◽  
Asymptotically Stable ◽  
Proliferation Response ◽  
Interaction Modeling ◽  
Stable Limit Cycles ◽  
Competing Populations

Tumoral dynamics and antitumor immunotherapies are likely to be influenced by the modalities of interaction between tumor cells and immune system effectors, and by the inter-effectors interactions. Within the framework of the theory of competing populations, we study here the influence of the proliferation response of effectors to tumor burden, and of cooperation and/or competition between immune system effectors, by means of three inter-related bi-dimensional meta-models. After studying their null-clines, we study the location and the local stability of the equilibria. Then, we investigate the existence and, in some cases, the uniqueness of stable limit cycles. The condition for the global asymptotically stable eradication under constant or slightly variable periodic immunotherapy is given. Finally, implications of strong saturation in the effectors ability to kill tumor cells are discussed.

scholarly journals Operating diagram of a flocculation model in the chemostat

2020 ◽  
Vol Volume 31 - 2019 - CARI 2018 ◽  
Author(s):  
Radhouane Fekih-Salem ◽  
Tewfik Sari
Keyword(s):  
Local Stability ◽  
Stability Region ◽  
Steady States ◽  
Complete Analysis ◽  
Stable Limit ◽  
Control Parameters ◽  
Coexistence Region ◽  
Microbial Ecosystem ◽  
International Audience ◽  
Stable Limit Cycles

International audience The objective of this study is to analyze a model of the chemostat involving the attachment and detachment dynamics of planktonic and aggregated biomass in the presence of a single resource. Considering the mortality of species, we give a complete analysis for the existence and local stability of all steady states for general monotonic growth rates. The model exhibits a rich set of behaviors with a multiplicity of coexistence steady states, bi-stability, and occurrence of stable limit cycles. Moreover, we determine the operating diagram which depicts the asymptotic behavior of the system with respect to control parameters. It shows the emergence of a bi-stability region through a saddle-node bifurcation and the occurrence of coexistence region through a transcritical bifurcation. Finally, we illustrate the importance of the mortality on the destabilization of the microbial ecosystem by promoting the washout of species. L'objectif de cette étude est d'analyser un modèle du chémostat impliquant la dynamique d'attachement et de détachement de la biomasse planctonique et agrégée en présence d'une seule ressource. En considérant la mortalité des espèces, nous donnons une analyse complète de l'existence et de la stabilité locale de tous les équilibres pour des taux de croissance monotones. Le modèle pré-sente un ensemble riche de comportements avec multiplicité d'équilibres de coexistence, bi-stabilité et apparition des cycles limites stables. De plus, nous déterminons le diagramme opératoire qui dé-crit le comportement asymptotique du système par rapport aux paramètres de contrôle. Il montre l'émergence d'une région de bi-stabilité via une bifurcation noeud col et l'occurrence d'une région de coexistence via une bifurcation transcritique. Enfin, nous illustrons l'importance de la mortalité sur la déstabilisation de l'écosystème microbien en favorisant le lessivage des espèces.

scholarly journals Stability and bifurcation analysis of a tumor-immune system with two delays and diffusion

2021 ◽  
Vol 19 (2) ◽  
pp. 1154-1173
Author(s):  
Yuting Ding ◽  
◽  
Gaoyang Liu ◽  
Yong An
Keyword(s):  
Immune System ◽  
Hopf Bifurcation ◽  
Tumor Cells ◽  
Multiple Time Scales ◽  
Multiple Time ◽  
Asymptotically Stable ◽  
Two Delays ◽  
The Stability ◽  
The Impact ◽  
And Diffusion

<abstract><p>A tumor-immune system with diffusion and delays is proposed in this paper. First, we investigate the impact of delay on the stability of nonnegative equilibrium for the model with a single delay, and the system undergoes Hopf bifurcation when delay passes through some critical values. We obtain the normal form of Hopf bifurcation by applying the multiple time scales method for determining the stability and direction of bifurcating periodic solutions. Then, we study the tumor-immune model with two delays, and show the conditions under which the nontrivial equilibria are locally asymptotically stable. Thus, we can restrain the diffusion of tumor cells by controlling the time delay associated with the time of tumor cell proliferation and the time of immune cells recognizing tumor cells. Finally, numerical simulations are presented to illustrate our analytic results.</p></abstract>

721 AT1412, a patient-derived CD9 antibody in preclinical development promoting tumor immune infiltration and inducing tumor rejection

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A763-A763
Author(s):  
Remko Schotte ◽  
Julien Villaudy ◽  
Martijn Kedde ◽  
Wouter Pos ◽  
Daniel Go ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Tumor Cells ◽  
Tumor Rejection ◽  
Human Immune System ◽  
Preclinical Development ◽  
High Affinity ◽  
Human Immune ◽  
A375 Melanoma

BackgroundAdaptive immunity to cancer cells forms a crucial part of cancer immunotherapy. Recently, the importance of tumor B-cell signatures were shown to correlate with melanoma survival. We investigated whether tumor-targeting antibodies could be isolated from a patient that cured (now 13 years tumor-free) metastatic melanoma following adoptive transfer of ex vivo expanded autologous T cells.MethodsPatient‘s peripheral blood B cells were isolated and tested for the presence of tumor-reactive B cells using AIMM’s immmortalisation technology. Antibody AT1412 was identified by virtue of its differential binding to melanoma cells as compared to healthy melanocytes. AT1412 binds the tetraspanin CD9, a broadly expressed protein involved in multiple cellular activities in cancer and induces ADCC and ADCP by effector cells.ResultsSpontaneous immune rejection of tumors was observed in human immune system (HIS) mouse models implanted with CD9 genetically-disrupted A375 melanoma (A375-CD9KO) tumor cells, while A375wt cells were not cleared. Most notably, no tumor rejection of A375-CD9KO tumors was observed in NSG mice, indicating that blockade of CD9 makes tumor cells susceptible to immune rejection.CD9 has been described to regulate integrin signaling, e.g. LFA-1, VLA-4, VCAM-1 and ICAM-1. AT1412 was shown to modulate CD9 function by enhancing adhesion and transmigration of T cells to endothelial (HUVEC) cells. AT1412 was most potently enhancing transendothelial T-cell migration, in contrast to a high affinity version of AT1412 or other high affinity anti-CD9 reference antibodies (e.g. ALB6). Enhanced immune cell infiltration is also observed in immunodeficient mice harbouring a human immune system (HIS). AT1412 strongly enhanced CD8 T-cell and macrophage infiltration resulting in tumor rejection (A375 melanoma). PD-1 checkpoint blockade is further sustaining this effect. In a second melanoma model carrying a PD-1 resistant and highly aggressive tumor (SK-MEL5) AT1412 together with nivolumab was inducing full tumor rejection, while either one of the antibodies alone did not.ConclusionsThe safety of AT1412 has been assessed in preclinical development and is well tolerated up to 10 mg/kg (highest dose tested) by non human primates. AT1412 demonstrated a half-life of 8.5 days, supporting 2–3 weekly administration in humans. Besides transient thrombocytopenia no other pathological deviations were observed. No effect on coagulation parameters, bruising or bleeding were observed macro- or microscopically. The thrombocytopenia is reversible, and its recovery accelerated in those animals developing anti-drug antibodies. First in Human clinical study is planned to start early 2021.Ethics ApprovalStudy protocols were approved by the Medical Ethical Committee of the Leiden University Medical Center (Leiden, Netherlands).ConsentBlood was obtained after written informed consent by the patient.

scholarly journals The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3596
Author(s):  
Reza Bayat Mokhtari ◽  
Manpreet Sambi ◽  
Bessi Qorri ◽  
Narges Baluch ◽  
Neda Ashayeri ◽  
...  
Keyword(s):  
Immune System ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Tumor Antigens ◽  
Response Rates ◽  
Viral Proteins ◽  
Tumor Rejection ◽  
Therapeutic Approaches ◽  
Patient Response ◽  
Specific Antigens

Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy.

A NONLINEAR DELAY MODEL DESCRIBING THE GROWTH OF TUMOR CELLS UNDER IMMUNE SURVEILLANCE AGAINST CANCER AND ITS STABILITY ANALYSIS

2012 ◽  
Vol 05 (03) ◽  
pp. 1260017 ◽  
Author(s):  
LING CHEN ◽  
WANBIAO MA
Keyword(s):  
Stability Analysis ◽  
Hopf Bifurcation ◽  
Periodic Solutions ◽  
Tumor Cells ◽  
Local Stability ◽  
Immune Surveillance ◽  
Delay Model ◽  
Existence Of Periodic Solutions ◽  
Growth Of Tumor ◽  
Nonlinear Delay

In this paper, based on some biological meanings and a model which was proposed by Lefever and Garay (1978), a nonlinear delay model describing the growth of tumor cells under immune surveillance against cancer is given. Then, boundedness of the solutions, local stability of the equilibria and Hopf bifurcation of the model are discussed in details. The existence of periodic solutions explains the restrictive interactions between immune surveillance and the growth of the tumor cells.

Response : Stable Limit Cycles in Prey-Predator Populations

Science ◽  
1973 ◽  
Vol 181 (4104) ◽  
pp. 1074-1074
Author(s):  
Robert M. May
Keyword(s):  
Limit Cycles ◽  
Stable Limit ◽  
Stable Limit Cycles
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