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Open AccessArticle

Novel Protein-Based Vaccine against Self-Antigen Reduces the Formation of Sporadic Colon Adenomas in Mice

1
AMAL Therapeutics, Fondation pour Recherches Médicales, 64 avenue de la Roseraie, 1205 Geneva, Switzerland
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Boehringer Ingelheim International GmbH, 55216 Ingelheim, Germany
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Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA
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Department of Pathology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA
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Blood Cell Development and Function Program, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA
*
Authors to whom correspondence should be addressed.
E.B. and A.A.L. share the first co-authorship.
M.L.C. and M.D. share the last co-authorship.
Academic Editor: Rafael Rosell
Cancers 2021, 13(4), 845; https://doi.org/10.3390/cancers13040845
Received: 5 February 2021 / Accepted: 11 February 2021 / Published: 17 February 2021
Colorectal cancer remains a leading cause of cancer-related mortality worldwide. However, high-risk populations with a genetic predisposition for colorectal cancer could benefit greatly from novel and efficacious immunopreventive strategies that afford long-lasting protection. The achaete-scute family bHLH transcription factor 2 (Ascl2) has been identified as a promising target for immunoprevention of colorectal cancer, based on its induction during the formation and progression of colorectal tumors and its minimal expression observed in healthy tissue. The goal of the present study was to determine the efficacy of a protein-based vaccine targeting Ascl2 in combination with an anti-PD-1 treatment in a spontaneous colorectal cancer mouse model. This novel vaccine strategy promotes potent tumor-specific immunity, and prevents the formation of colon adenomas in mice. The results demonstrate that Ascl2 is a promising target for immunoprevention for individuals at elevated risk of developing colorectal cancer.
Novel immunopreventive strategies are emerging that show great promise for conferring long-term protection to individuals at high risk of developing colorectal cancer. The KISIMA vaccine platform utilizes a chimeric protein comprising: (1) a selected tumor antigen; (2) a cell-penetrating peptide to improve antigen delivery and epitope presentation, and (3) a TLR2/4 agonist to serve as a self-adjuvant. This study examines the ability of a KISIMA vaccine against achaete-scute family bHLH transcription factor 2 (Ascl2), an early colon cancer antigen, to reduce colon tumor formation by stimulating an anti-tumor immune response. Vaccine administrations were well-tolerated and led to circulating antibodies and antigen-specific T cells in a mouse model of colorectal cancer. To assess preventive efficacy, the vaccine was administered to mice either alone or in combination with the immune checkpoint inhibitor anti-PD-1. When delivered to animals prior to colon tumor formation, the combination strategy significantly reduced the development of colon microadenomas and adenomas, as compared to vehicle-treated controls. This response was accompanied by an increase in the intraepithelial density of CD3+ T lymphocytes. Together, these data indicate that the KISIMA-Ascl2 vaccine shows great potential to be a safe and potent immunopreventive intervention for individuals at high risk of developing colorectal cancer. View Full-Text
Keywords: cancer vaccine; colon cancer; mouse model; Ascl2; T cell response; humoral response cancer vaccine; colon cancer; mouse model; Ascl2; T cell response; humoral response
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MDPI and ACS Style

Belnoue, E.; Leystra, A.A.; Carboni, S.; Cooper, H.S.; Macedo, R.T.; Harvey, K.N.; Colby, K.B.; Campbell, K.S.; Vanderveer, L.A.; Clapper, M.L.; Derouazi, M. Novel Protein-Based Vaccine against Self-Antigen Reduces the Formation of Sporadic Colon Adenomas in Mice. Cancers 2021, 13, 845. https://doi.org/10.3390/cancers13040845

AMA Style

Belnoue E, Leystra AA, Carboni S, Cooper HS, Macedo RT, Harvey KN, Colby KB, Campbell KS, Vanderveer LA, Clapper ML, Derouazi M. Novel Protein-Based Vaccine against Self-Antigen Reduces the Formation of Sporadic Colon Adenomas in Mice. Cancers. 2021; 13(4):845. https://doi.org/10.3390/cancers13040845

Chicago/Turabian Style

Belnoue, Elodie; Leystra, Alyssa A.; Carboni, Susanna; Cooper, Harry S.; Macedo, Rodrigo T.; Harvey, Kristen N.; Colby, Kimberly B.; Campbell, Kerry S.; Vanderveer, Lisa A.; Clapper, Margie L.; Derouazi, Madiha. 2021. "Novel Protein-Based Vaccine against Self-Antigen Reduces the Formation of Sporadic Colon Adenomas in Mice" Cancers 13, no. 4: 845. https://doi.org/10.3390/cancers13040845

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