Treating Diffuse Large B Cell Lymphoma Using HLA Class I Molecule Deficient Anti CD19 CAR-NK Cells

Student: Suraj Das
Table: MED10
Experimentation location: Home
Regulated Research (Form 1c): No
Project continuation (Form 7): No

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Abstract:

Bibliography/Citations:

 

Bibliography:

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Additional Project Information

Project website: -- No project website --
Additional Resources: -- No resources provided --
 

Research Plan:

 

  • This project is completely research-based, and all of my experimental evidence comes from similar experiments conducted by various labs. Below is a rough outline of my paper, which describes all the topics I did research on to develop my treatment
    • Introduction
      • The immune system
        • Adaptive Immunity
          • T Cells
          • B Cells
        • Innate Immunity
          • Nk Cells
        • Cluster of Differentiation
      • Major Histocompatibility Complex
        • MHC mismatch regulation
      • Chimeric Antigen Receptors
        • CAR Receptor design and structure
        • Types of CAR-cells
        • Shortcomings of CAR cells
      • Lymphoma
        • Non-Hodgkin’s Lymphoma 
          • Diffuse Large B-cell Lymphoma
            • Current treatments
              • Shortcomings
              • Advantages
        • Lymphoma classification

 

  • CRISPR Cas9 Gene Editing Technology
    • Type II CRISPR systems
    • Previous ways CRISPR has been used in the medical field

 

  • Nk Cell Sources
    • Induced Pluripotent Stem Cells
    • Human Pluripotent Stem Cells
  • Cell Design
    • Advantageous genes to inhibit function of in NK cells
      • Pd-1 inhibiting receptor
    • CAR-receptor structure to use
  • Experimental Design

 

  • Functional Assays

 

  • Conclusion

 

 

 

 

 

Questions and Answers

1. What was the major objective of your project and what was your plan to achieve it? 

I desired to make a possible treatment for Diffuse Large B-cell lymphoma that would be capable of overcoming some of the disadvantages current treatments for the disease have.

       a. Was that goal the result of any specific situation, experience, or problem you encountered?  

This goal was not the result of any situation I personally experienced, however, it was the result of an accumulation of experiences in varous fields of science that made me more and more interested in the entire field of medical treatment and how CRISPR Cas9 can be used to treat different cancers.

 

 

       b. Were you trying to solve a problem, answer a question, or test a hypothesis?

I was trying to develop a hypothetical solution to my hypothesis. Unfortunately, because of the funding that is required to actually conduct such an experiment properly, it is not feasible to test my hypothesis. I can only use data from already conducted experiments to create my own solution.

 

2. What were the major tasks you had to perform in order to complete your project?

      There were three major tasks that I needed to complete - background research, experiment, and cell design, and my conclusion. My background research comprised of all the biological topics related to CRISPR Cas9, the immune system, and lymphoma. For further information, see my research plan. My experiment and cell design consisted of my hypothetical CAR-Nk cell structure, as well as the process for creating it.

 

3. What is new or novel about your project?

       a. My project is entirely unique in the fact that it integrates cell designs from other various experiments, as well as using some original and novel cell designs proposed by me. Primarily, I have conducted two rounds of CRISPR Cas9 gene editing to knock out two different genes that are highly related to Diffuse Large B-cell Lymphoma(DLBCL). Most other treatments have only used one round of gene editing, however in my case I chose to use two because I believe that using such a cell design will increase the Nk cell's targeting capability of malignant B-cells, and also its ability to bypass the HLA mismatch restriction.

 

4. What was the most challenging part of completing your project?

      The most challenging part of my project was completing the cell design and experimental method, simply because it is very difficult to decide where to start; there is such a vast amount of information regarding my topic. My treatment also had to be something that was overcoming some of the flaws in modern-day treatments, so that added to the difficulty level somewhat.

 

5. If you were going to do this project again, are there any things you would you do differently the next time?

If there is something I would have liked to do differently, it would probably be to have the opportunity to observe CRISPR Cas9 gene-editing technology first-hand. This is something that I was not able to do, and I feel as though having such an experience would definitely be helpful for modifying my perspective on CRISPR Cas9 and CAR therapies.

 

6. Did working on this project give you any ideas for other projects? 

This project also created a new possible research topic for me to explore, which is the creation of Induced Pluripotent Stem Cells. The research I did on them for this project made me realize that there is still much work to do in the field to determine the optimal source of stem cells, and I am quite interested in some of the different ways we can develop induced pluripotent stem cells. An example of this would be keratinocyte-based stem cells, which is a source for stem cells that have not been researched extensively but seems to have incredible potential in the medical field.

 

7. How did COVID-19 affect the completion of your project?

COVID-19 did not really affect the completion of my project, because the large majority of my project was completed through online research, so I did not struggle too much with my project, fortunately.