Alternative tumour-specific antigens

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Tumour-specific antigens (TSAs) are crucial for developing targeted antitumour therapies.
• Non-synonymous single-nucleotide variant (SNV) neoantigens are the most studied class of TSAs.
• Expanding the repertoire of therapeutic targets necessitates exploring alternative TSA sources.

Purpose of the Study:

• To review alternative tumour antigens derived from non-SNV genomic alterations.
• To discuss the biology, detection tools, and clinical relevance of these alternative TSAs.
• To highlight challenges and solutions for the clinical translation of alternative TSA-based therapies.

Main Methods:

• Literature review and synthesis of current research on alternative TSAs.
• Analysis of biological mechanisms underlying alternative TSA generation.
• Evaluation of computational tools for identifying alternative TSAs.
• Review of preclinical and clinical studies involving alternative TSAs.

Main Results:

• Alternative TSAs arise from various non-SNV sources, including frameshifts, splice variants, and gene fusions.
• Some alternative TSAs are shared across multiple tumors, offering potential for universal therapies.
• Computational tools and preclinical/clinical studies are emerging for alternative TSA evaluation.

Conclusions:

• Alternative TSAs represent a promising avenue for expanding cancer immunotherapy targets.
• The shared nature of some alternative TSAs could lead to 'off-the-shelf' therapeutic strategies.
• Overcoming current challenges is key to realizing the clinical potential of alternative TSAs.