Exploration of Targeted Anti-tumor Therapy

Table 1. Comparison of tumor antigen classes and their vaccination pros/cons.

Antigen type	Examples	Definition	Pros of vaccination	Cons of vaccination
Tumor-associated antigens (TAAs)	MUC1, HER2, prostate acid phosphatase (PAP), MAGE-A, NY-ESO-1	Self-antigens overexpressed or aberrantly expressed in tumors but are also found at low levels in normal tissue	- Broadly shared across patients - Suitable for “off-the-shelf” vaccines - Scalable manufacturing	- Subject to immune tolerance - Weak immunogenicity - Risk of autoimmunity if expressed in normal tissues
Neoantigens	KRAS G12D, TP53 R175H, BRAF V600E, PIK3CA E545K, EWS-FLI1, PAX7-FOXO1 fusions	Non-self antigens arising from somatic mutations or gene fusions unique to tumor cells	- High immunogenicity - No central tolerance - Personalized and tumor-specific - Lower off-target risk	- Individualized production (time-consuming and costly) - Requires tumor sequencing and prediction - May miss escape variants
Cryptic/Hidden antigens (e.g., fusion breakpoints)	EWSR1 exon 7-FLI1 fusion (e.g., “SQQSSSYGQQ...”)	Peptides derived from untranslated regions, aberrant transcripts, or fusion breakpoints absent from the normal proteome	- Highly specific to tumors - Potential “public” neoantigens in some sarcomas - May be shared across subsets of patients	- Limited validation - Often unknown expression/presentation - Technical difficulty in identification and prediction

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Author contributions

PJV: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. The author read and approved the submitted version.

Conflicts of interest

Panagiotis J. Vlachostergios, who is the Guest Editor of Exploration of Targeted Anti-tumor Therapy, had no involvement in the decision-making or the review process of this manuscript.

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