CD70 overexpression

However, validation through in vitro and in vivo experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.

Finally, we also demonstrated that treatment with the hypomethylating agent azacytidine can drive increased CD70 expression, similar to that shown in AML models. Taken together, targeting CD70 appears to be a highly promising cellular therapeutic strategy for MM, with particularly high utility in high-risk patients after BCMA CAR-T relapse. We are continuing preclinical and future clinical development of this CAR-T strategy, using our natural ligand CD27 design with extended in vivo persistence.

Moreover, different monoclonal antibodies (Abs) and Ab-derivates were tested including a CD70 blocking antibody (αCD70) and an antibody-dependent cell-mediated cytotoxicity (ADCC) optimized antibody (cusatuzumab, ArgenX) that activates FcγR-expressing effector cells to assess the therapeutic potential of targeting CD70 in MM... Our results indicate that CD70-expressing MM cells have a stem-cell like phenotype and propagate the disease. Targeting CD70 is a promising new therapy especially in advanced disease.

In this regard, different Abs and Ab-derivates were tested including a CD70 blocking antibody (αCD70) and an antibody-dependent cell-mediated cytotoxicity (ADCC) optimized antibody (cusatuzumab) that activates FcγR-expressing effector cells... Although the treatment options of MM have rapidly increased during the last years, MM remains an incurable disease that ultimately leads to death. Our results indicate that especially advanced MM stages express high levels of CD70. In addition, our results indicate that CD70/CD27 cell-autonomous signaling contributes to disease progression and therapy resistance and identifies CD70 as potential target in MM.

In summary, the highly potent anti-tumor activity in multiple tumor types and wide therapeutic index of ARX305 support clinical evaluation of this next generation anti-CD70 ADC. ARX305 is currently in a Phase 1 dose escalation study in China, and the IND in the United States is open.

This study identified actionable immunotherapy targets which could inform future comparative oncology trials in canine OSCC: CTLA-4, PD-1, CXCL2. These data provide a good first step towards utilizing spontaneous canine OSCC as a comparative model for human OSCC radiation and immuno-oncology research.

Our results provide evidence on the pivotal roles of CD70 and ZEB1 in immune escape in mNSCLC, suggesting that EMT might promote cancer progression and metastasis by not only increasing cancer cell plasticity but also reprogramming the immune response in the local tumor microenvironment.

In vivo, the anti-tumor activity of CD70-targeted TRuC-T cells was significantly improved by IL-15fu in multiple tumor models and was associated with enhanced intratumoral T-cell accumulation and a preferential expansion of CD8+ T cells. Conclusions The addition of the IL-15fu improved the phenotype, persistence, and anti-tumor activity of CD70-targeted TRuC-T cells, potentially increasing the likelihood of clinical benefit in patients with CD70 overexpressing solid and liquid cancers.

CD27 was expressed with moderate to strong intensity in 76% of cases. Overall, our results suggest that SOX11 expression in MCL is associated with an immunosuppressive microenvironment characterized by CD70 overexpression in tumor cells, increased Treg cell infiltration and downmodulation of antigen-processing and -presentation and T-cell activation that could promote MCL progression and represent a potential target for tailored therapies.