Mathematical Modeling of Anti-Tumor Vaccinotherapy: The Interaction of Immune System with Tumor Cells

2019 ◽  
Author(s):  
E. A. Kuzina ◽  
N. A. Babushkina
Keyword(s):  
Mathematical Modeling ◽  
Immune System ◽  
Tumor Cells

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.

Multifunctional biomimetic nanoparticles loading baicalin for polarizing tumor-associated macrophages

Nanoscale ◽  
2019 ◽  
Vol 11 (42) ◽  
pp. 20206-20220 ◽  
Author(s):  
Shulan Han ◽  
Wenjie Wang ◽  
Shengfang Wang ◽  
Shuo Wang ◽  
Ruijun Ju ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Immune Tolerance ◽  
Drug Efficacy ◽  
Tumor Associated Macrophages ◽  
Biomimetic Nanoparticles

Immunosuppression and immune tolerance lead tumor cells to evade immune system surveillance and weaken drug efficacy.

scholarly journals An update on clinical oncology for the non-oncologist

2016 ◽  
Vol 14 (2) ◽  
pp. 294-299
Author(s):  
Rafael Aliosha Kaliks
Keyword(s):  
Public Health ◽  
Immune System ◽  
Health System ◽  
Cancer Treatment ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Public Health System ◽  
Developed Countries ◽  
Driver Mutations ◽  
New Treatments

ABSTRACT Recent advances in the understanding of tumor driver mutations, signaling pathways that lead to tumor progression, and the better understanding of the interaction between tumor cells and the immune system are revolutionizing cancer treatment. The pace at which new treatments are approved and the prices at which they are set have made it even more difficult to offer these treatments in countries like Brazil. In this review we present for the non-oncologist these new treatments and compare their availability in Brazilian public health system and private health system with that of developed countries.

Application of Nanocomposites in Cancer Immunotherapy

Nano LIFE ◽  
2017 ◽  
Vol 07 (03n04) ◽  
pp. 1750008
Author(s):  
Wenhan Liu ◽  
Zejun Wang ◽  
Yao Luo ◽  
Nan Chen
Keyword(s):  
Immune System ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Critical Role ◽  
Clinical Advances ◽  
Review Current

Despite the clinical advances in oncology, cancer is still the major cause of death worldwide. Recent research demonstrates that the immune system plays a critical role in preventing tumor occurrence and development. The focus on cancer treatment has been shifted from directly targeting the tumor cells to motivating the immune system to achieve this goal. However, the activity of immune system is often suppressed in cancer patients. To boost the anti-tumor immunity against cancers, various nanocomposites have been developed to enhance the efficacy of immunostimulatory agents. Here, we review current advances in nanomaterial-mediated immunotherapy for the treatment of cancer, with an emphasis on applications of nanocomposites as immunoadjuvants in cancer therapy.

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.

DISCRETE KINETIC CELLULAR MODELS OF TUMORS IMMUNE SYSTEM INTERACTIONS

1996 ◽  
Vol 06 (08) ◽  
pp. 1187-1209 ◽  
Author(s):  
M. LO SCHIAVO
Keyword(s):  
Immune System ◽  
Computational Complexity ◽  
Differential Equations ◽  
Statistical Mechanics ◽  
Tumor Cells ◽  
Kinetic Modelling ◽  
Immune Defence ◽  
Control Parameters ◽  
Cellular Models ◽  
The One

This paper deals with a kinetic modelling of the cellular dynamics of tumors interacting with an active immune defence system. The analysis starts from the model proposed in Refs. 4 and 5 where a kinetic (cellular) theory of the interactions and competition between tumor cells and immune system is developed in a framework similar to the one of nonlinear statistical mechanics. The class of models proposed in this paper replaces the system of integro-differential equations by a system of ordinary differential equations. This has several advantages. Firstly, it allows immediate interpretations of the control parameters and is characterized by a relatively lower computational complexity. Further, some interesting periodicity properties of the solutions are characterized.

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