TIL therapy

Question 1

What are the differences between TIL, TCR engineered T cell and CAR T

Answer 1

• TIL → recognize a broad spectrum of antigens
• TCR T cells → recognize antigens presented on an HLA molecule
• CAR T cells → recognize antigen on the surface of the cell (HLA-independent) (CD19, CD22)

Question 2

Explain about the Rosenberg Protocol!

Answer 2

1. Surgical removal and fragmentation of the tumor tissue to harvest TILs.
2. Rapid expansion protocol of TILs in the lab using Interleukin-2 (IL-2).
3. Lymphodepleting chemotherapy before reinfusion to reduce immune suppression.
4. Reinfusion of expanded TILs, followed by high-dose IL-2 to enhance T cell survival and activity.

Question 3

Describe the advantages and disadvantages of TIL therapy

Answer 3

Advantages:
- Its diverse TCR clonality
- Superior tumor-homing ability
- Low off-target toxicity

Disadvantages:
- - Therapy not as effective as non-immunogenic tumors
- Only a minority of TILs are truly reactive to neoantigens and bystander T cell overgrowth during rapid expansion
- Unclear identification and isolation of neo-antigen specific lymphocytes during selection process
- Immunosuppressive TME → exhaustion of infiltrating cytotoxic T cells

Question 4

Characteristics of neoantigen in comparison to TAA

Answer 4

• Tumor specific → advantage
• Patient specific → disadvantage
• Neoantigens is usually derived from ‘passenger mutations’
  
  • Driver mutation → BRAF → hardly ever lead to a T cell response
  • Padahal bagus ya kalo dibuat jadi TCR yg recognize BRAF untuk treat 50% melanoma yang punya BRAF mutations, tapi ya sulit membentuk respon T cell