Immunization With Placenta-Specific 1 (Plac1) Induces Potent Anti-Tumor Responses and Prolongs Survival in a Mouse Model of Melanoma Publisher Pubmed



Rahdan S¹ ; Razavi SA¹ ; Shojaeian S² ; Shokri F¹ ; Amiri MM¹ ; Zarnani AH^{1, 3}
Source: Advances in Medical Sciences Published:2022

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) ​+ ​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. © 2022 Medical University of Bialystok