Drug-induced response and antibody-dependent cellular cytotoxicity in microfluidic cultures with dynamic flow
(2021) KIMM05 20202Department of Immunotechnology
- Abstract
- Current in-vitro models for mantle cell lymphoma (MCL) are standardized 2D cell cultures. These models do not incorporate the complexities seen in the human body 3D environment such as dynamic fluid flow or mechanical stress which are known to affect cellular behavior. MCL is a subtype of Non-Hodgkin’s lymphoma (NHL) with a poor prognosis often involving relapses and the overall survival is low. For current treatments there is a heterogeneity in patient response making personalized treatment predictions highly sought for. In this report, a microfluidic culture system which takes aspects such as dynamic flow and mechanical stresses into consideration, is used to establish an in-vivo like model for MCL. The model is evaluated for drug... (More)
- Current in-vitro models for mantle cell lymphoma (MCL) are standardized 2D cell cultures. These models do not incorporate the complexities seen in the human body 3D environment such as dynamic fluid flow or mechanical stress which are known to affect cellular behavior. MCL is a subtype of Non-Hodgkin’s lymphoma (NHL) with a poor prognosis often involving relapses and the overall survival is low. For current treatments there is a heterogeneity in patient response making personalized treatment predictions highly sought for. In this report, a microfluidic culture system which takes aspects such as dynamic flow and mechanical stresses into consideration, is used to establish an in-vivo like model for MCL. The model is evaluated for drug response studies by examining cell proliferation in the presence of the targeted drug Venetoclax, specifically targeting Bcl-2. Additionally, co-culturing experiments using MCL cells, patient-obtained peripheral blood mononuclear cells (PBMC) and CD20 targeting antibodies Rituximab and Obinutuzumab have been evaluated with the intention of generating antibody-dependent cellular cytotoxicity (ADCC). It was found that the microfluidic culture system showed promise as a model for drug response studies even though the significance of the results must be further validated. ADCC was observed in the co-culture setup and the two methods of analysis, flow cytometry and confocal imaging, showed similar results. This points to the methods being interchangeable for this endeavour, but results must be confirmed with more replicates. For future experiments an incorporation of the co-culture setup in the microfluidic culture system is envisioned. (Less)
- Popular Abstract
- Predicting cancer treatments on-chip
Cancer is one of the most common causes of death in our modern society. Billions of dollars are spent on cancer research each year, but the concept of “curing cancer” has so far been an elusive dream. One reason for this is the numerous types of cancer, as it is the collective name for when genetic abnormalities result in tumor growth, and that they cannot all be treated in the same way. For our thesis work we are interested in a lymphoma (blood cancer) subtype - mantle cell lymphoma (MCL). It is a rare disease, but with poor prognosis. One of the problems for MCL is that patients respond differently to the same treatments. This makes it difficult to know which therapy is the best one and to predict... (More) - Predicting cancer treatments on-chip
Cancer is one of the most common causes of death in our modern society. Billions of dollars are spent on cancer research each year, but the concept of “curing cancer” has so far been an elusive dream. One reason for this is the numerous types of cancer, as it is the collective name for when genetic abnormalities result in tumor growth, and that they cannot all be treated in the same way. For our thesis work we are interested in a lymphoma (blood cancer) subtype - mantle cell lymphoma (MCL). It is a rare disease, but with poor prognosis. One of the problems for MCL is that patients respond differently to the same treatments. This makes it difficult to know which therapy is the best one and to predict what the outcome will be for the patient. Developing a method that can accurately predict the required treatment type for a specific patient would minimize suffering associated with going through difficult treatments; that in the end might not even work.
Currently the models used for testing drugs are cells grown outside the body in simple containers. To better simulate the human body environment we manufactured a simple chip. This microfluidic chip has a chamber in which cells are cultured and a channel with an active flow that represents fluid flows in our bodies. To evaluate how the cells in these chips respond to an anti-cancer drug, we analyzed cell behavior. This was done by using different staining dyes that give information on how much cells have divided or on how much cells have died. It was found that drug-treated cells divided less and died more. In the future we believe that tests like this could be run in parallel with many different drugs.
The human body is not only a complex 3D environment, it also contains immune cells that affect the efficiency of biological drugs, such as antibodies. We have made initial investigations to simulate this process by using a culture with MCL cells, therapeutic antibodies and immune cells extracted from patient blood. These three components are known to work together to kill cancerous cells and this could be seen in our experiments. In the future we hope to incorporate this in our microfluidic model. In conclusion, with more experiments we hope that this could become a successful model for evaluating possible treatments for MCL. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9041070
- author
- Hedberg, Ellinor LU and Hjelmgren, Linn LU
- supervisor
-
- Sara Ek LU
- Lavanya Lokhande LU
- organization
- course
- KIMM05 20202
- year
- 2021
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Microfluidics, Mantle cell lymphoma, in-vitro model, hydrogel, cell culture system
- language
- English
- id
- 9041070
- date added to LUP
- 2021-03-04 12:08:18
- date last changed
- 2021-03-04 12:08:18
@misc{9041070,
abstract = {{Current in-vitro models for mantle cell lymphoma (MCL) are standardized 2D cell cultures. These models do not incorporate the complexities seen in the human body 3D environment such as dynamic fluid flow or mechanical stress which are known to affect cellular behavior. MCL is a subtype of Non-Hodgkin’s lymphoma (NHL) with a poor prognosis often involving relapses and the overall survival is low. For current treatments there is a heterogeneity in patient response making personalized treatment predictions highly sought for. In this report, a microfluidic culture system which takes aspects such as dynamic flow and mechanical stresses into consideration, is used to establish an in-vivo like model for MCL. The model is evaluated for drug response studies by examining cell proliferation in the presence of the targeted drug Venetoclax, specifically targeting Bcl-2. Additionally, co-culturing experiments using MCL cells, patient-obtained peripheral blood mononuclear cells (PBMC) and CD20 targeting antibodies Rituximab and Obinutuzumab have been evaluated with the intention of generating antibody-dependent cellular cytotoxicity (ADCC). It was found that the microfluidic culture system showed promise as a model for drug response studies even though the significance of the results must be further validated. ADCC was observed in the co-culture setup and the two methods of analysis, flow cytometry and confocal imaging, showed similar results. This points to the methods being interchangeable for this endeavour, but results must be confirmed with more replicates. For future experiments an incorporation of the co-culture setup in the microfluidic culture system is envisioned.}},
author = {{Hedberg, Ellinor and Hjelmgren, Linn}},
language = {{eng}},
note = {{Student Paper}},
title = {{Drug-induced response and antibody-dependent cellular cytotoxicity in microfluidic cultures with dynamic flow}},
year = {{2021}},
}