ROPN1B (Ropporin-1B) is a tumor-associated antigen classified as a cancer-testis antigen (CTA), exhibiting restricted expression in normal tissues but widespread presence in malignancies . As a paralog of ROPN1 (96% sequence homology), ROPN1B is implicated in oncogenic processes, including cell migration and metastasis, via interactions with RhoA signaling pathways . While not yet developed as a therapeutic antibody, its immunogenicity has been validated through endogenous antibody responses in cancer patients .
ROPN1B demonstrates robust expression in melanoma and triple-negative breast cancer (TNBC), making it a candidate for targeted therapies.
Advanced Disease Correlation: ROPN1B expression increases with melanoma progression (73.1% in early stages vs. 100% in late stages) .
ROPN1B elicits strong humoral immunity, particularly in metastatic melanoma patients.
| Parameter | Melanoma Patients | TNBC Patients |
|---|---|---|
| Antibody Prevalence | 71.2% (74/104) | Not reported |
| Disease Stage Association | Higher in advanced | High expression |
| Comparison to NY-ESO-1 | ROPN1B | NY-ESO-1 |
| Early-stage expression | 73.1% | 3.8% |
| Late-stage expression | 100% | 31.0% |
Antibodies against ROPN1B are detectable in sera/plasma, suggesting tumor-specific immune recognition .
ROPN1B’s immunogenicity is attributed to its cancer-restricted expression and lack of tolerance in immune-privileged sites (e.g., testis) .
While no therapeutic ROPN1B antibody has been developed, its properties make it a prime target for:
Multi-Antigen Combinations: Pairing ROPN1B with NY-ESO-1 or differentiation antigens (e.g., TYR/MLANA) could enhance tumor coverage .
Epitope Selection: Peptides like FLY-1A/1B (HLA-A2-restricted) show promise for T-cell activation .
TCR-Engineered T Cells: Preclinical models demonstrate efficacy of ROPN1-targeted T cells in TNBC and melanoma organoids .
Safety Profile: Minimal on-target toxicity due to ROPN1B’s absence in adult healthy tissues .
| Antigen | Expression in TNBC | Homogeneity | Immune Privilege |
|---|---|---|---|
| ROPN1B | >90% | High | Testis/epididymis |
| NY-ESO-1 | 16% | Low | Testis |
| MAGE-A4 | 25% | Moderate | Testis |