Modi-2 a vaccine stimulating CD4 responses to homocitrullinated self epitopes as therapy for solid cancers

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Tumour microenvironment stress can modify self-proteins, creating neoepitopes like homocitrulline.
• Homocitrullination bypasses self-tolerance, presenting a target for cancer immunotherapy.
• Hydrophobic peptides used in vaccines pose manufacturing and solubility challenges.

Purpose of the Study:

• To assess a novel vaccine targeting homocitrullinated antigens for anti-tumour immunity.
• To utilize self-assembling nanoparticle technology (SNAPvax™) for optimized vaccine delivery.
• To evaluate the manufacturing ease and T cell induction of the Modi-2 vaccine.

Main Methods:

• Developed Modi-2, a vaccine using SNAPvax™ to co-deliver four homocitrullinated peptides and adjuvant.
• Designed nanoparticles for precise size and composition, optimizing manufacturing and T cell responses.
• Tested Modi-2 efficacy in preclinical mouse models of melanoma, colorectal, and breast cancer.

Main Results:

• Modi-2 demonstrated strong T cell responses and significant anti-tumour immunity in B16 melanoma, CT26 colorectal, and 4T1 breast cancer models.
• The vaccine formulation proved effective in stimulating a robust immune response against established tumours.
• Target antigens for Modi-2 were found to be expressed in human lung, colorectal, breast, and prostate tumours.

Conclusions:

• The Modi-2 vaccine, utilizing SNAPvax™ technology, effectively stimulates anti-tumour immunity.
• Modi-2 shows promise for treating multiple cancer types, including melanoma, colorectal, and breast cancer.
• The vaccine's potential for clinical translation in various cancer indications is supported by preclinical data.