This study provides important insights into how the use of active drug PK assays, coupled with mechanistic follow-up, can inform and enable ongoing benefit/risk assessment for individuals participating in FIH dose-escalation trials. Translational studies that lead to a better understanding of the underlying biology of cognate T- and B-cell interactions, ultimately resulting in ADA development to novel biotherapeutics, are needed.

Our study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNβ-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen.

P1, N=12, Active, not recruiting, Mayo Clinic | Trial completion date: Apr 2024 --> Jan 2027 | Trial primary completion date: Apr 2024 --> Jan 2027

P1, N=12, Active, not recruiting, Mayo Clinic | Trial completion date: Apr 2023 --> Apr 2024 | Trial primary completion date: Apr 2023 --> Apr 2024

While OV response alone is not sufficient for clinical benefit, the evidence of epitope spreading is encouraging. Future studies of VSV-IFNb-TYRP1 will evaluate combinations with other therapies.

P1, N=20, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | Trial completion date: Jan 2023 --> Jul 2022 | Trial primary completion date: Jan 2023 --> Jul 2022

P1, N=72, Suspended, Mayo Clinic | Trial completion date: Mar 2022 --> Apr 2023 | Recruiting --> Suspended | Trial primary completion date: Mar 2022 --> Apr 2023

P1, N=20, Active, not recruiting, Hoffmann-La Roche | N=310 --> 20

P1, N=310, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1, N=310, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2023 --> Jan 2023 | Trial primary completion date: Sep 2023 --> Jan 2023

The expression of genes related to melanin synthesis, such as tyrosinase, tyrosinase-related protein-1, tyrosinase-related protein-2, and microphthalmia-associated transcription factor, also supports these phenomena, which means that even in the presence of resveratrol, grape extract will strengthen the function of α-MSH in promoting melanin synthesis. Therefore, these results also provide a point of view for research on cosmetics.

Thus, miR155HG silencing inhibited the malignant biological behavior of OC cells by targeting the miR-155-5p/TYRP1 axis. The present study provides novel insights into the underlying mechanism of OC progression.