Blockade of CTLA-4 promotes the development of effector CD8+ T lymphocytes and the therapeutic effect of vaccination with an attenuated protozoan expressing NY-ESO-1.
The development of cancer immunotherapy has long been a challenge. Here, we report that prophylactic vaccination with a highly attenuated Trypanosoma cruzi strain expressing NY-ESO-1 (CL-14-NY-ESO-1) induces both effector memory and effector CD8(+) T lymphocytes that efficiently prevent tumor development. However, the therapeutic effect of such a vaccine is limited. We also demonstrate that blockade of Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) during vaccination enhances the frequency of NY-ESO-1-specific effector CD8(+) T cells producing IFN-γ and promotes lymphocyte migration to the tumor infiltrate. As a result, therapy with CL-14-NY-ESO-1 together with anti-CTLA-4 is highly effective in controlling the development of an established melanoma.
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, 30190-002, Brazil.
Luara Isabela
LI
Dos Santos
Bruno
B
Galvão-Filho
Paula Cristina
PC
de Faria
Caroline
C
Junqueira
Miriam Santos
MS
Dutra
Santuza Maria Ribeiro
SM
Teixeira
Maurício Martins
MM
Rodrigues
Gerd
G
Ritter
Oliver
O
Bannard
Douglas Thomas
DT
Fearon
Lis Ribeiro
LR
Antonelli
Ricardo Tostes
RT
Gazzinelli
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology / Q000469:parasitology / Q000628:therapy*; D008565:Membrane Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins; D011994:Recombinant Proteins