A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation
Su He Wang1,2, Zhengyi Cao3, Mohammad Farazuddin3,4
1Michigan Nanotechnology Institute for Medicine and Biological Sciences, Medical School, University of Michigan, Ann Arbor, MI, 48109, USA. shidasui@umich.edu.
Abstract:
KRAS mutations occur commonly in the lung and can lead to the development of non-small cell lung cancer (NSCLC). While the mutated KRAS protein is a neoantigen, it usually does not generate an effective anti-tumor immune response on mucosal/epithelial surfaces. Despite this, mutated KRAS remains a potential target for immunotherapy since immune targeting of this protein in animal models has been effective at eliminating tumor cells. We attempted to develop a KRAS vaccine using mutated and wild-type KRAS peptides in combination with a nanoemulsion (NE) adjuvant. The efficacy of this approach was tested in an inducible mutant KRAS-mouse lung tumor model. Animals were immunized intranasally using NE with KRAS peptides. These animals had decreased CD4+FoxP3+ T cells in both lymph nodes and spleen. Immunized animals also showed higher IFN-γ and IL-17a levels to mutated KRAS that were produced by CD8+ T cells and enhancement in KRAS-specific Th1 and Th17 responses that persisted for 3 months after the last vaccination. Importantly, the immunized animals had significantly decreased tumor incidence compared to control animals. In conclusion, a mucosal approach to KRAS vaccination demonstrated the ability to induce local KRAS-specific immune responses in the lung and resulted in reduced tumor incidence.
Insights
A novel intranasal KRAS peptide vaccine with a nanoemulsion adjuvant reduced non-small cell lung cancer (NSCLC) incidence in mice. This approach successfully induced local immune responses in the lungs, highlighting its potential for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- KRAS mutations are frequent drivers in non-small cell lung cancer (NSCLC).
- Mutated KRAS proteins are neoantigens but typically fail to elicit effective anti-tumor immunity at mucosal surfaces.
- Targeting mutated KRAS via immunotherapy shows promise, as demonstrated in preclinical models.
Purpose of the Study:
- To develop and evaluate a KRAS peptide-based vaccine delivered via a mucosal route.
- To assess the vaccine's efficacy in an inducible mutant KRAS-driven mouse lung tumor model.
- To investigate the induced immune responses and their impact on tumor development.
Main Methods:
- Development of a vaccine using mutated and wild-type KRAS peptides combined with a nanoemulsion (NE) adjuvant.
- Intranasal immunization of mice in an inducible mutant KRAS lung tumor model.
- Analysis of immune cell populations (e.g., CD4+FoxP3+ T cells) and cytokine production (IFN-γ, IL-17a) from CD8+ T cells.
Main Results:
- Immunization led to a reduction in CD4+FoxP3+ T cells in lymphoid organs.
- Elevated IFN-γ and IL-17a levels specific to mutated KRAS were observed, produced by CD8+ T cells.
- Sustained KRAS-specific Th1 and Th17 responses persisted for 3 months post-vaccination.
- Significantly decreased tumor incidence was observed in vaccinated animals compared to controls.
Conclusions:
- A mucosal vaccination strategy targeting KRAS can induce localized immune responses in the lung.
- This approach effectively reduced tumor incidence in a preclinical lung cancer model.
- Intranasal KRAS peptide vaccination represents a potential therapeutic strategy for NSCLC.
More Related Videos
Related Concept Videos
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists