T-CELL BASED ADOPTIVE IMMUNOTHERAPY

Question 1

First kind of T-cell based adoptive immunotherapy and DLI

Answer 1

HSCT
DLI: avoid GVHD and favor GVT
Alternative strategies of DLI

Question 2

TCR editing

Answer 2

Pros and cons
Further evolution with the gene editing CRISPR-Cas9 technology
Main problem: choose the tumor-specific antigen

Question 3

Suicide genes to switch off T cells

Answer 3

Herpes simplex virus tymidine kinase
Inducible Cas9

Question 4

CAR-T cells

Answer 4

Chimeric antigen receptor
Components and structure of CAR
Evolution: different generations
Advantages
Disadvantages: only surface molecules
Sequential steps for the development of CAR-T cells: selection of scFv with best affinity, choice of the space, screening of co-stimulatory domains, pay attention to the size to avoid immunogenicity
First clinical trial
CD19
Challenges in solid tumours
Safety problems: dual targeting split receptor system