Immunization with placenta-specific 1 (plac1) induces potent anti-tumor responses and prolongs survival in a mouse model of melanoma.
Adv Med Sci
; 67(2): 338-345, 2022 Sep.
Article
em En
| MEDLINE
| ID: mdl-36084365
ABSTRACT
PURPOSE:
Melanoma is a malignant and metastatic form of skin cancer, which is not diagnosed in early stages of the disease. Nowadays, immunotherapy is changing the treatment landscape for metastatic melanoma. Placenta-specific1 (PLAC1) is a cancer-testis-placenta (CTP) antigen with differential expression in melanoma tissues. Here, we evaluated the potential of plac1 to induce anti-cancer immune responses as well as to prevent cancer development in a mouse model of melanoma.METHODS:
Two proteins containing full extracellular domain (ED) of mouse plac1+KDEL3 and full ED of mouse plac1+ tetanus toxin P2 and P30+ pan DR epitope (PADRE) â+ âKDEL3 were produced and injected in mice to evaluate their capacity to induce anti-cancer immune responses as well as their potential to prevent melanoma development. Induction of plac1-specific humoral and cellular responses as well as tumor-associated parameters were tested in a series of 36 mice.RESULTS:
Sera of mice immunized with ED â+ âP2P30+PADRE â+ âKDEL3 contained antibodies able to react with surface plac1 in B16F10 âcells. Both proteins induced proliferative cellular immune responses against B16F10 âcells and plac1-specific cytotoxic T cells (CTL) and CD107a â+ âCTL responses, which was higher in mice immunized with ED â+ âP2P30+PADRE â+ âKDEL3. Splenocytes of mice vaccinated with ED â+ âP2P30+PADRE â+ âKDEL3 exerted a significant cytotoxicity against B16F10 âcells. Vaccination with ED â+ âP2P30+PADRE â+ âKDEL3 significantly delayed B16F10-induced tumor onset, reduced tumor growth, and increased survival. Tumors induced by B16F10 expressed plac1 in vivo.CONCLUSION:
Our results pave the way for development of effective melanoma preventive vaccine in humans, although further studies are needed.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Gravidez
/
Vacinas Anticâncer
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Melanoma
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Adv Med Sci
Assunto da revista:
MEDICINA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Irã