T cell receptor grafting allows virological control of Hepatitis B virus infection.
J Clin Invest
; 129(7): 2932-2945, 2019 04 30.
Article
en En
| MEDLINE
| ID: mdl-31039136
ABSTRACT
T cell therapy is a promising means to treat chronic HBV infection and HBV-associated hepatocellular carcinoma. T cells engineered to express an HBV-specific T cell receptor (TCR) may achieve cure of HBV infection upon adoptive transfer. We investigated the therapeutic potential and safety of T cells stably expressing high affinity HBV envelope- or core-specific TCRs recognizing European and Asian HLA-A2 subtypes. Both CD8+ and CD4+ T cells from healthy donors and from chronic hepatitis B patients became polyfunctional effector cells when grafted with HBV-specific TCRs and eliminated HBV from infected HepG2-NTCP cell cultures. A single transfer of TCR-grafted T cells into HBV-infected, humanized mice controlled HBV infection and virological markers declined 4-5 log or below detection limit. When - as in a typical clinical setting - only a minority of hepatocytes were infected, engineered T cells specifically cleared infected hepatocytes without damaging non-infected cells. Cell death was compensated by hepatocyte proliferation and alanine amino transferase levels peaking at day 5 to 7 normalized again thereafter. Co-treatment with the entry inhibitor Myrcludex B ensured long-term control of HBV infection. Thus, T cells stably transduced with highly functional TCRs have the potential to mediate clearance of HBV-infected cells causing limited liver injury.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
2_ODS3
/
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
1_doencas_transmissiveis
/
2_enfermedades_transmissibles
/
4_hepatitis
/
6_digestive_diseases
Asunto principal:
Receptores de Antígenos de Linfocitos T
/
Linfocitos T CD4-Positivos
/
Virus de la Hepatitis B
/
Linfocitos T CD8-positivos
/
Hepatitis B Crónica
/
Hígado
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Clin Invest
Año:
2019
Tipo del documento:
Article
País de afiliación:
Alemania