VTCN1 overexpression

Interestingly, the distance from B7-H4+ cells to the nearest CD8+ cells was significantly farther in patients dying from cancer after surgery or immune checkpoint inhibitors compared to cancer survivors; thus, high B7-H4 expression in tumor cells may inhibit CD8 infiltration into the tumor space and that B7-H4-positive cells form a specific spatial niche. In summary, we performed a comprehensive evaluation of B7 family member expression and found that the spatial distribution of B7-H4 suggests the potentially useful role of combination blockade with both B7-H4 and the current anti-PD-1/PD-L1 axis in the treatment of UC.

Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.

P1, N=30, Terminated, Pfizer | Trial completion date: Jan 2024 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2024 --> Oct 2023; Pfizer has made an internal business decision to not continue further development of PF-07260437. This decision was not due to major safety concerns or requests from any regulatory authorities.

These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC and provide evidence for activity of an ADC with a DNA-damaging payload in this population.

P1, N=25, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=100 --> 25 | Trial completion date: Sep 2025 --> Jan 2024 | Trial primary completion date: Sep 2025 --> Jan 2024

In summary, these results suggested that ECA inhibits B7-H4 expression via STAT3 inhibition, leading to SPC/TGF-β1-induced EMT. Therefore, ECA might be an immune oncological drug for B7-H4-positive cancer, especially lung cancer.

XMT-1660 is a B7-H4-directed Dolasynthen antibody drug conjugate designed with a precise, optimized drug-to-antibody ratio and a DolaLock microtubule inhibitor payload with controlled bystander effect. NCT05377996. Clinical trial information: NCT05377996.

These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC.

P1, N=100, Recruiting, Pfizer | Trial completion date: Mar 2025 --> Sep 2025 | Trial primary completion date: Mar 2025 --> Sep 2025

B7-H4 may represent a potential biomarker for the diagnosis and prognosis of CRC and enhance CRC invasion by promoting EMT.

The trial is currently enrolling patients. NCT05377996

VTCN1 is a co-inhibitory molecule which negatively regulates T-cell immune response and promotes immune escape. The association between genetic mutations in cancer cells and the immune status in the tumor microenvironment may suggest potential treatment with combination targeted therapy plus immunotherapy.