Preprint Article Version 1 This version is not peer-reviewed

Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response Against Melanoma Tumor

Version 1 : Received: 28 July 2018 / Approved: 30 July 2018 / Online: 30 July 2018 (06:13:44 CEST)

A peer-reviewed article of this Preprint also exists.

Rajendrakumar, S.K.; Mohapatra, A.; Singh, B.; Revuri, V.; Lee, Y.-K.; Kim, C.S.; Cho, C.-S.; Park, I.-K. Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response against Melanoma Tumor. Polymers 2018, 10, 1063. Rajendrakumar, S.K.; Mohapatra, A.; Singh, B.; Revuri, V.; Lee, Y.-K.; Kim, C.S.; Cho, C.-S.; Park, I.-K. Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response against Melanoma Tumor. Polymers 2018, 10, 1063.

Journal reference: Polymers 2018, 10, 1063
DOI: 10.3390/polym10101063

Abstract

Malignant melanoma is a highly aggressive type of cancer that requires radical treatment strategies to inhibit the cancer cell progression and metastasis. In recent years, preclinical research and clinical trials on melanoma treatment are considerably focused on the adjuvant-based immunotherapy for enhancing the immune response of innate immune cells against cancer cells. However, the clinical outcome of these adjuvant-based treatments are inadequate due to improper delivery system for these immune activators to reach the target site. Hence, we developed a vaccine formulation containing tumor lysate protein (TL) and poly I:C (PIC) complexed with positively charged poly (sorbitol-co- polyethylenimine (PEI)(PSPEI). The resulting ionic PSPEI-polyplexed antigen/adjuvant (PAA) (PSPEI-PAA) nanocomplexes were stable at the physiological condition, non-toxic and  enhanced intracellular uptake in immature dendritic cells. In murine B16F10 tumor xenograft model, PSPEI-PAA nanocomplexes significantly suppressed tumor growth and did not exhibit any noticeable sign of toxicity. Additionally, the cytotoxic T lymphocytes (CTLs) assay involving co-culturing of splenocytes isolated from the PSPEI-PAA-treated mice with that of B16F10 cells significantly revealed enhanced cancer killing by the TL-reactivated CTLs compared to untreated control mice bearing tumor. Therefore, we strongly believe that PSPEI-PAA nanocomplexes could be an efficient antigen/adjuvant delivery system and also enhance the antitumor immune response against melanoma tumor in the future clinical trials.

Subject Areas

poly I:C; adjuvant; antigen; melanoma; polyethylenimine; immunotherapy

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