Optimized dithranol-imiquimod-based transcutaneous immunization enables tumor rejection.

Area of Science:

• Immunology
• Vaccinology
• Dermatology

Background:

• Transcutaneous immunization (TCI) is a non-invasive vaccination strategy that elicits robust cellular immunity, vital for cancer rejection.
• The DIVA (dithranol/IMQ based vaccination) platform combines imiquimod (IMQ) and dithranol for TCI, previously showing promise.
• Further optimization of the DIVA platform focused on drug dosage, application methods, and a new IMQ formulation.

Purpose of the Study:

• To optimize the DIVA transcutaneous immunization platform for enhanced T cell responses and cancer immunotherapy.
• To investigate the impact of adjuvant dose, application site, and order on immune responses and inflammation.
• To evaluate a new nanocrystalline imiquimod formulation (IMI-Sol+) for improved storage and application.

Main Methods:

• C57BL/6 mice were immunized with ovalbumin-derived peptides using dithranol and IMQ ointments applied to ear skin.
• T cell responses were quantified using flow cytometry and IFN-γ ELISpot assays.
• Local skin inflammation was assessed by measuring ear swelling.

Main Results:

• Optimal T cell priming required co-localization of adjuvants and peptide antigens on the skin.
• Dithranol's application order was critical for superior T cell responses, while IMQ formulation (IMI-Sol+) improved handling without compromising efficacy.
• DIVA boosted antigen-specific T cells and memory responses significantly, with double treatment providing complete tumor protection in a prophylactic model.

Conclusions:

• Optimized DIVA transcutaneous immunization generates potent cellular immune responses crucial for effective tumor growth control.
• This enhanced TCI method demonstrates significant potential for clinical development as a non-invasive cancer vaccine strategy.