PMID- 34048178
OWN - NLM
STAT- MEDLINE
DCOM- 20211125
LR  - 20211125
IS  - 2476-762X (Electronic)
IS  - 1513-7368 (Print)
IS  - 1513-7368 (Linking)
VI  - 22
IP  - 5
DP  - 2021 May 1
TI  - Reverse Vaccinology Approach in Constructing a Multi-Epitope Vaccine Against 
      Cancer-Testis Antigens Expressed in Non-Small Cell Lung Cancer.
PG  - 1495-1506
LID - 89599 [pii]
LID - 10.31557/APJCP.2021.22.5.1495 [doi]
AB  - BACKGROUND: The 5-year survival rate of non-small cell lung cancer (NSCLC) 
      patients has not significantly improved despite advancements in the currently 
      applied treatments. Thus, efforts are put forth in developing novel 
      immunotherapeutic agents targeting cancer-testis antigens (CTA) in NSCLC. This 
      work utilized reverse vaccinology approach in designing a novel multi-epitope 
      vaccine targeting melanoma-associated antigen 3 (MAGEA3), MAGEA4, New York 
      esophageal squamous cell carcinoma-1 (NY-ESO-1), and Kita-Kyushu lung cancer 
      antigen 1 (KK-LC1), being the most frequently expressed CTAs in NSCLC. METHODS: 
      Epitopes were mapped from the sequences of CTAs. The population coverage (PC) of 
      identified CD4+ and CD8+ epitopes were estimated. Candidate linear B cell (BL), 
      CD4+, and CD8+ epitopes were adjoined in a multi-epitope construct (Mvax) with 
      flagellin domain as an adjuvant. Antigenicity, and cross-reactivity of Mvax were 
      examined. The tertiary structure of Mvax was modelled, and validated. All 
      epitopes included in the vaccine were docked with their human leukocyte antigen 
      (HLA) binders. The immunogenicity of epitopes in Mvax was validated through 
      molecular dynamics analysis. RESULTS: Mvax contains 22 epitopes from MAGEA3, 
      MAGEA4, NY-ESO-1, and KK-LC1. It is classified as antigenic, non-allergen, 
      non-toxic, and possesses physicochemical stability. Epitopes have no significant 
      hits with other human proteins, except for 2 other CTAs frequently expressed in 
      NSCLC. The stretch of BL epitopes in Mvax confers flexibility, and accessibility 
      emphasizing its antigenicity. The tertiary structure analysis showed that Mvax 
      model has good structural quality. All epitopes included in the vaccine are 
      highly immunogenic as indicated by favorable binding affinity, low binding 
      energy, and acceptable root-mean-square deviation (RMSD). CD4+ and CD8+ epitopes 
      have global PC of 81.81%, and 84.15%, respectively. CONCLUSION: Overall, in 
      silico evaluations show that Mvax is a potential immunotherapeutic agent against 
      NSCLC.
FAU - Herrera, Leana Rich M
AU  - Herrera LRM
AUID- ORCID: 0000 - 0003 - 2243 - 2747
AD  - Department of Physical Sciences, College of Science, Polytechnic University of 
      the Philippines, Manila City, Philippines.
LA  - eng
PT  - Journal Article
DEP - 20210501
PL  - Thailand
TA  - Asian Pac J Cancer Prev
JT  - Asian Pacific journal of cancer prevention : APJCP
JID - 101130625
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (CT83 protein, human)
RN  - 0 (CTAG1B protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (MAGEA3 protein, human)
RN  - 0 (MAGEA4 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Antigens, Neoplasm/*immunology
MH  - Cancer Vaccines/administration & dosage/*immunology
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/*immunology/metabolism/pathology
MH  - Epitopes/*immunology
MH  - Humans
MH  - Lung Neoplasms/drug therapy/*immunology/metabolism/pathology
MH  - Membrane Proteins/immunology
MH  - Neoplasm Proteins/immunology
MH  - Vaccinology/*methods
PMC - PMC8408400
OTO - NOTNLM
OT  - In Silico
OT  - Keywords: NSCLC
OT  - cancer-testis antigen
OT  - reverse vaccinology
COIS- Author has no conflict of interest to declare.
EDAT- 2021/05/29 06:00
MHDA- 2021/11/26 06:00
PMCR- 2021/07/01
CRDT- 2021/05/28 13:26
PHST- 2021/02/06 00:00 [received]
PHST- 2021/05/28 13:26 [entrez]
PHST- 2021/05/29 06:00 [pubmed]
PHST- 2021/11/26 06:00 [medline]
PHST- 2021/07/01 00:00 [pmc-release]
AID - 89599 [pii]
AID - 10.31557/APJCP.2021.22.5.1495 [doi]
PST - epublish
SO  - Asian Pac J Cancer Prev. 2021 May 1;22(5):1495-1506. doi: 
      10.31557/APJCP.2021.22.5.1495.