Optimized Dose of Dendritic Cell-based Vaccination in Experimental Model of Tumor Using Artificial Neural Network

Abstract

Previous studies have demonstrated that maturation of dendritic cells (DCs) by pathogenic components through pathogen-associated molecular patterns (PAMPs) such as Listeria monocytogenes lysate (LML) or CpG DNA can improve cancer vaccination in experimental models. In this study, a mathematical model based on an artificial neural network (ANN) was used to predict several patterns and dosage of matured DC administration for improved vaccination.
 The ANN model predicted that repeated co-injection of tumor antigen (TA)-loaded DCs matured with CpG (CpG-DC) and LML (List-DC) results in improved antitumor immune response as well as a reduction of immunosuppression in the tumor microenvironment. In the present study, we evaluated the ANN prediction accuracy about DC-based cancer vaccines pattern in the treatment of Wehi164 fibrosarcoma cancer-bearing mice.
 Our results showed that the administration of the DC vaccine according to ANN predicted pattern, leads to a decrease in the rate of tumor growth and size and augments CTL effector function. Furthermore, gene expression analysis confirmed an augmented immune response in the tumor microenvironment.
 Experimentations justified the validity of the ANN model forecast in the tumor growth and novel optimal dosage that led to more effective treatment.

Exosomes Derived from Heat‐shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells

“…The non-adherent or loosely adherent cells were collected on day 6 and then transferred to another well for maturation. 2,25…”

“…DCs would then be able to arouse T cells by presenting texosome-MHC molecules. 5 Antigens from texosomes can be processed and delivered by MHC I / II molecules, as well as by overexpressing co-stimulatory molecules. Additionally, transferred texosome mRNAs could be translated in DCs to produce and present tumor antigens.…”

Emerging Strategies of Engineering and Tracking Dendritic Cells for Cancer Immunotherapy

“…One study optimizing a dendritic cell vaccine through obtaining an optimized dose/number of administered DCs used a mathematical model based on an artificial neural network (ANN). 87 This study used error between the tumor size in the desired day and the output of the network to train ANN, then ANN predicted tumor size at desired day. It simulated several injection profiles by trial and error to find the optimal pattern to minimize the size of the tumor in the final days.…”

“…We need to find other methods to improve the therapeutic efficacy of DC vaccines. One study optimizing a dendritic cell vaccine through obtaining an optimized dose/number of administered DCs used a mathematical model based on an artificial neural network (ANN) . This study used error between the tumor size in the desired day and the output of the network to train ANN, then ANN predicted tumor size at desired day.…”