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Tomato lectin-modified nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine: Targeting intestinal M
Pan Long1, Qian Zhang2, Mingtao Xue2
1Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China; Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, PR China.
Abstract:
Vaccines administered orally enable the stimulation of both the mucous membrane and system immune responses. However, tumor vaccines, whose effective elements are antigen protein molecules or gene-encoding antigens, are hardly accustomed to the harsh gastrointestinal environment. Here, we explored an oral nanoecapsulated tumor vaccine complex to evaluate the anti-tumor effect. Tomato lectin (TL) was modified on the surface of a nanoemulsion (NE) composed of MAGE1-HSP70/SEA (MHS). C57BL/6 mice were immunized with NE (-), NE (MHS) and TL-NE (MHS) via po. or sc. administration. Additionally, the cellular immunocompetence was detected by the enzyme-linked immunospot assay and lactate dehydrogenase release assay. Serum antibody titers were analyzed using the enzyme-linked immuno sorbent assay. Next, the therapeutic and tumor challenge assays were performed. The TL-NE (MHS) particles were 20 ± 5 nm in diameter and could resist pepsin and trypsin digestion. The cellular immune responses elicited by TL-NE (MHS) perioral were stronger than those by TL-NE (MHS)-sc. (p < 0.05) when targeted to B16-MAGE1 tumor cells. The levels of MAGE-1 antibody induced by TL-NE (MHS) via the oral route was higher than control group (p < 0.05). The percentage of CD4+ and CD8+ T cells in TL-NE (MHS)-po. group was more than other groups (p < 0.05). Furthermore, oral TL-NE (M)HScould delay tumor growth and defer tumor occurrence and tumor recurrence after resection in mice challenged with B16-MAGE-1 tumor cells. The study suggested that the oral TL-NE (MHS) vaccine delivery system is feasible to improve the vaccine protection effect and may have broad application in cancer therapy.
Insights
An oral nanoencapsulated tumor vaccine using tomato lectin (TL) resists digestion and enhances immune responses. This novel delivery system shows promise for delaying tumor growth and recurrence in mice.
Area of Science:
- Biotechnology
- Immunology
- Nanomedicine
Background:
- Oral vaccines stimulate mucosal and systemic immunity but face challenges in the gastrointestinal environment.
- Tumor vaccines using antigen proteins or genes are vulnerable to degradation in the digestive tract.
Purpose of the Study:
- To explore an oral nanoencapsulated tumor vaccine complex for evaluating anti-tumor effects.
- To assess the efficacy of a tomato lectin (TL)-modified nanoemulsion (NE) containing MAGE1-HSP70/SEA (MHS) for oral cancer vaccination.
Main Methods:
- Tomato lectin (TL) was surface-modified onto a nanoemulsion (NE) of MAGE1-HSP70/SEA (MHS).
- C57BL/6 mice were immunized orally (po.) or subcutaneously (sc.) with NE, NE (MHS), or TL-NE (MHS).
- Immune responses were assessed via ELISpot, LDH release assay, serum antibody titers, and T cell analysis (CD4+, CD8+). Therapeutic and tumor challenge assays were conducted.
Main Results:
- TL-NE (MHS) particles (20±5 nm) resisted pepsin and trypsin digestion.
- Oral TL-NE (MHS) elicited stronger cellular immune responses than subcutaneous administration.
- Higher MAGE-1 antibody titers and increased CD4+/CD8+ T cell percentages were observed with oral TL-NE (MHS).
- Oral TL-NE (MHS) delayed tumor growth, occurrence, and recurrence in mice challenged with B16-MAGE-1 cells.
Conclusions:
- The oral TL-NE (MHS) vaccine delivery system is feasible for enhancing vaccine protection.
- This nanoencapsulated oral vaccine demonstrates significant anti-tumor effects and potential for broad application in cancer therapy.
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