CAR T-Cell Therapy Lecture Notes

Introduction

• CAR T-cell therapy: An individualized treatment for cancer.
• T-cells: Reprogrammed to express CAR (Chimeric Antigen Receptor) specifically to fight cancer cells.

Importance of T-Cells

• Role: Crucial in the immune system.
• Function: Mount a response against viral infections and recognize/eliminate cancer cells.
• Issue: Cancer cells may develop mechanisms to evade immune defense.

Solution

• Objective: Find antigens unique to the surface of cancer cells.
• CAR T-Cells: Modified to detect specific antigens on cancer cells, maintaining their natural T-cell receptors.
• Mechanism: Use a key-lock principle to match tumor antigen with cytotoxic functions to eliminate cancer cells.

Differentiation

• Key Difference: CAR T-cells vs. Natural T-cells — CAR T-cells have an added chimeric antigen receptor.

CAR T-Cell Manufacturing Process

1. Blood Collection: Patient's blood is collected, T-cells isolated and cultured.
2. Genetic Modification:
   • Viral vector (e.g., lentivirus) is used to carry CAR gene.
   • Viral Transduction: T-cells are infected with lentivirus, inserting the CAR gene.
   • Expression: After transcription and translation, CAR protein receptors are produced.
3. Cell Expansion: CAR T-cell population expanded in the lab.
4. Infusion: Expanded CAR T-cells are infused back into the patient.

Mechanism of Action Inside the Patient

• Patrolling: CAR T-cells patrol the body to find tumor cells with specific antigens (e.g., CD19).
• Recognition and Activation: CAR T-cells recognize cancer cells and downstream signaling is activated.
• Cancer Cell Elimination: Common mode involves cytokine release which kills cancer cells.

Conclusion

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