Project Title: Building "Off-the Shelf" CAR T-cells
BASIS Advisor: Mr. Davoren
Internship Location: Columbia University (remote)
Onsite Mentor: Dr. Hans-Willem Snoeck
My Posts
Final Remarks
Many thanks to my faculty advisor Mr. Davoren and my on-site advisor Dr. Hans Snoeck for all their support in this project. You can view my future work (including my podcast) by visiting and subscribing to my personal blog, Brooklyn Musings. You can also follow me on Twitter @SidR73. Thank you! Final Conclusions “Off-the-Shelf” CAR […]
Week 12: Examining Different Perspectives and Building a Podcast
Hello! This week I’ll discuss the interviews I conducted as part of my senior project. I had the privilege of talking with Dr. Hans Snoeck and Dr. Mamonkin this month. I’m very grateful that they took the time to speak with me on CAR T-cells and the immune system. Interview with Dr. Hans Snoeck Dr. […]
Week 11: Investigating the Potential of iNKT Cells
Hello! This week I’ll be discussing Invariant Natural Killer T cells and how they relate to building “Off-the-Shelf” CAR T-cells. Invariant Natural Killer Cells Invariant Natural Killer T cells are natural killer cells that possess a semi-invariant T cell protein receptor, a receptor that is genetically identical to every human. iNKTs make up less than […]
Week 10: The Promise of CAR-NK Cells
Hello! This week I’ll discuss how to engineer “off-the-shelf” CAR-NK cells and why they might be a better alternative to CAR T-cells. CAR T-cells have been successful in treating leukemias and lymphomas. However, it is important to investigate CAR-NK cells which may have a similar therapeutic potential, safer side effects, and a better ability to […]
Week 9: Pseudo-Homozygous HLA Cells
Hello! This week I’ll revisit HLA matching and discuss strategies of engineering HLA-matched cells for “Off-the-Shelf” CAR T-cells. Why is HLA matching necessary? Human Leukocyte Antigens (HLA) are responsible for helping the immune system distinguish itself from foreign bodies. When cells with foreign HLA genes are found in the immune system, they are attacked by […]
Week 8: Cytosine Base Editing and Beam-201
Hello! I’m Sidharth, and this week I’ll be discussing cytosine base editing and a newly published “Off-the-Shelf” CAR T-cell method. Cytosine Base Editing Gene editing techniques are required to create allogeneic CAR T-cells. However, many of these techniques have flaws that can unintentionally disrupt the order of the DNA. Transcription activator-like effector nucleases (TALENS) are […]
Week 7: A “Double Agent”
Hello! I’m Sidharth, and this week I’ll discuss the PD-1 Signal Transduction Pathway and the Beta 2 Microglobulin protein and their role in cancer. The Programmed Cell Death 1 (PD-1) Signal Transduction Pathway PD-1 is a double agent: it’s an important immuno-regulatory protein (protecting us from autoimmune diseases), however when cancer attacks our body, it […]
Week 6: Stealing Cancer’s Mighty Shield
Hello! This week I’ll be discussing Induced Pluripotent Stem Cells (iPSCs) and CD47, cancer’s mighty shield. Induced Pluripotent Stem Cells Induced Pluripotent Stem Cells (iPSCs) are blood or skin cells that are reprogrammed into a pluripotent stem cell state (i.e., they can self-renew and differentiate into any cell of the body). Four protein transcription factors, […]
Week 5: The Alloimmune Defense Receptor System
Hello! I’m Sidharth, and this week I’ll explain and evaluate a new method of creating “Off-the-Shelf” CAR T-cells that was first proposed two years ago by Dr. Maksim Mamonkin. In July 2020, scientists at Baylor University published an intriguing paper detailing a novel way to create “Off-the-Shelf” CAR T-cells. Can these cells surmount the adversities […]
Week 4: A Deep Dive Into HLA Matching
Hello! I’m Sidharth, and this week I’ll be discussing HLA matching and analyzing transplant studies in an attempt to prevent “Off-the-Shelf” CAR T-cells from inducing dangerous immune responses. Problem: In order to forge “Off-the-Shelf” CAR T-cells, HLA matching is required to avoid a potentially lethal immune response. Exactly how much HLA matching is needed? Human […]
Video: Killer T Cells In Action
The immune system is immensly powerful and beautiful. Above is a video of a killer T cell destroying an ovarian cancer cell, captured by a spinning disc confocal microscope. This process takes about an hour, but the video has been sped up. What’s happening? The killer T cell (pictured in purple to the left) attaches […]
Week 3: T Cell Receptors and Invariant Natural Killer T Cells
Hello! My name is Sidharth, and this week I’ll discuss the role of T cell receptors (TCRs) in the immune system and in “off-the-shelf” CAR T-cells. What are T cell receptors? T cell receptors (TCRs) are protein complexes that are found on the surface of T cells. They recognize antigens (proteins from pathogens) that are […]
Week 2: Human Leukocyte Antigens and iPS Cells
Hello! My name is Sidharth. This week I’ll be exploring induced pluripotent stem cells and human leukocyte antigens to continue laying the foundations for “off-the-shelf” CAR T-cells. The HLA Bank Human Leukocyte Antigens (HLA) are one of the keys to unlocking the power of “off-the-shelf” CAR T-cells. As mentioned last week, engineered CAR T-cells must […]
Week 1: A Complex Defense System
Hello! My name is Sidharth, and this week I’ll be discussing our bodies’ complex defense system against pathogens that “off-the-shelf” CAR T-cells must overcome. How do Major Histocompatibility Complexes work? Major Histocompatibility Complexes (MHC) are crucial to our bodies’ defense system against pathogens. They are protein receptors that appear on the membranes of cells. MHC […]
Week 0: Introduction
Hello! I’m Sidharth Raghavan, and over the next ten weeks, I will be researching different ways to build “Off-the-Shelf” CAR T-cells. I was first introduced to CAR T-cells during a lecture series at Memorial Sloan Kettering Cancer Center in 2020. Learning about the discoveries that paved the way for this groundbreaking treatment inspired me to […]