Immunization with placenta-specific 1 (plac1) induces potent anti-tumor responses and prolongs survival in a mouse model of melanoma.
Advances in medical sciences(2022)
摘要
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) + KDEL3 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 + P2P30+PADRE + KDEL3 contained antibodies able to react with surface plac1 in B16F10 cells. Both proteins induced proliferative cellular immune responses against B16F10 cells and plac1-specific cytotoxic T cells (CTL) and CD107a + CTL responses, which was higher in mice immunized with ED + P2P30+PADRE + KDEL3. Splenocytes of mice vaccinated with ED + P2P30+PADRE + KDEL3 exerted a significant cytotoxicity against B16F10 cells. Vaccination with ED + P2P30+PADRE + KDEL3 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.
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