Engineering T Cells. Mack Cash

Transcription

1 Engineering T Cells Mack Cash

2 Background Info T Cells Determine a response to antigens in the body Differentiate into different subsets of T cells Ex: Memory, Helper, Regulatory, etc. Regulate and kill harmful cells in body Antigens Substance capable of stimulating a immune response Ex: Virus, Bacteria, Cancer cell, etc. Receptor: Molecule on surface of T Cell Responsible for recognizing specific antigen

3 CAR T cells T cells engineered with chimeric antigen receptors Processed by using disabled virus to encode the cell September 20, 2017, by NCI Staff, September 11, 2017, by NCI Staff, and August 31, 2017, by Matthew Goetz, M.D. "FDA Approves Second CAR T-Cell Therapy." National Cancer Institute. N.p., n.d. WebWhitesides GM. Whitesides group: write a paper. Advanced Materials 16(15): , 2004.

4 Structure The CAR T cell has three layers Ectodomain Transmembrane Domain Endodomain Zhang, Cheng, Jun Liu, Jiang F. Zhong, and Xi Zhang. "Engineering CAR-T Cells." Biomarker Research 5.1 (2017): n. pag.

5 Ectodomain Sits outside the cytoplasm Contains several key features: Signal peptide Antigen recognition region Spacer

6 Transmembrane Domain Consists of a hydrophobic alpha helix that spans the membrane

7 Endodomain Functional end of the receptor Signals the T cell when antigen is recognized

8 Implementation 1. Obtain a blood sample from the patient 2. Filter T cells from sample 3. Modify and multiply T cells 4. Reinfuse patient with newly engineered T cells

9 Challenges Cytokine Release Syndrome (CRS) Cytokines are secreted by T cells during antigen detection to help signal other white blood cells (including more T cells) Creates a positive feedback loop in which cytokines and white blood cells storm the area Causes inflammation and can be fatal if left untreated Determining healthy cells from cancer cells Healthy cells and cancer cells do share several antigens Can gate receptors by looking for multiple antigens, or shutting the signal off if a healthy one is detected

10 Receptors as Gates Srivastava, Shivani, and Stanley R. Riddell. "Engineering CAR-T Cells: Design Concepts." Trends in Immunology 36.8 (2015):

11 Pros / Cons Pros CAR T cells remain in the system long after treatment, making them lifelong cancer drugs Treatment was exceptional in leukemia and lymphoma trials with an incredible success rate Cons CRS Killing healthy cells Very expensive procedure Further research is still required

12 What Does the Future Hold? On August 30 th, the FDA approved the first CAR T cell therapy On October 18 th, the FDA cleared a different type of CAR T cell therapy Research is being done on how to attack solid tumors

13 Works Cited 1. Posey, Avery D., Carl H. June, and Bruce L. Levine. "Cancer Killers." Scientific American (2017): September 20, 2017, by NCI Staff, September 11, 2017, by NCI Staff, and August 31, 2017, by Matthew Goetz, M.D. "FDA Approves Second CAR T-Cell Therapy." National Cancer Institute. N.p., n.d. WebWhitesides GM. Whitesides group: write a paper. Advanced Materials 16(15): , Srivastava, Shivani, and Stanley R. Riddell. "Engineering CAR-T Cells: Design Concepts." Trends in Immunology 36.8 (2015): Zhang, Cheng, Jun Liu, Jiang F. Zhong, and Xi Zhang. "Engineering CAR-T Cells." Biomarker Research 5.1 (2017): n. pag.