Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response against Melanoma Tumor
Authors: Bijay Singh
In-Kyu Park
Yong-Kyu Lee
Chong-Su Cho
Adityanarayan Mohapatra
Santhosh Kalash Rajendrakumar
Chang Seong Kim
Vishnu Revuri
Journal: Polymers (2018)
Discipline: CHEMISTRY
Keywords: adjuvant; antigen; immunotherapy; melanoma; poly I:C
Affiliations: Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, Korea. ., Research Institute for Bioscience and Biotechnology, Nakkhu-4, Lalitpur 44600, Nepal. ., Department of Green Bioengineering, Korea National University of Transportation, Chungju 27469, Korea. ., Department of Internal Medicine, Chonnam National University Medical School, 42 Jebongro, Gwangju 501-757, Korea. ., Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. .

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 have been 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 is inadequate due to an 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, are non-toxic, and have enhanced intracellular uptake of antigen and adjuvant in immature dendritic cells leading to dendritic cell maturation. In the murine B16F10 tumor xenograft model, PSPEI-PAA nanocomplexes significantly suppressed tumor growth and did not exhibit any noticeable sign of toxicity. The level of matured dendritic cells (CD80+/CD86+ cells) in the tumor draining lymph node of PSPEI-PAA treated tumor mice were enhanced and therefore CD8+ T cells infiltration in the tumor were enriched. 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 enhance the antitumor immune response against melanoma tumor in the future clinical trials. 

Retracted: No

PubPeer comments:
 Marked quadrants are different from the control!! ![file] , 
 We understand that the flow cytometry plot axis was different between the control and the treatment groups in figure 5a. The error has been rectified. However, the correction didn t affect the current results and conclusions![file] ,