Immunization with placenta-specific 1 (plac1) induces potent anti-tumor responses and prolongs survival in a mouse model of melanoma.

Shaghayegh Rahdan, Seyed Alireza Razavi, Sorour Shojaeian, Fazel Shokri, Mohammad Mehdi Amiri, Amir-Hassan Zarnani

Advances in medical sciences 2022 Sep

filter terms:

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. 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. 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. Our results pave the way for development of effective melanoma preventive vaccine in humans, although further studies are needed. Copyright © 2022 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Citation

Shaghayegh Rahdan, Seyed Alireza Razavi, Sorour Shojaeian, Fazel Shokri, Mohammad Mehdi Amiri, Amir-Hassan Zarnani. 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 Sep;67(2):338-345