Selected Articles from This Issue

The study addresses challenges in CD38-targeted therapies for multiple myeloma and lymphomas. The novel bispecific antibody, VP301, effectively targets CD38 and ICAM-1 on tumor cells, with reduced red blood cell binding compared to daratumumab. VP301 demonstrates potent ADCC and ADCP activities, even in cases of low CD38 expression. Promising efficacy is observed in myeloma and lymphoma models, with notable synergistic effects in combination with lenalidomide. This innovative approach provides a potential solution to overcome resistance and relapse seen with current CD38 therapies, presenting a new avenue for treating multiple myeloma and lymphoma in cancer science.

N-terminal processing by methionine aminopeptidases (MetAP) is critical for protein maturation. Friese-Hamim and colleagues report the characterization of the novel, potent, selective, reversible small molecule MetAP2 inhibitor, M8891. M8891 monotherapy blocks human endothelial cell growth and differentially inhibits cancer cell growth to cause robust angiogenesis and tumor growth inhibition. Combining M8891 with VEGF receptor inhibition causes tumor stasis/regression in renal cell carcinoma (RCC) patient-derived xenograft models, particularly those that are p53 wild-type, had Von Hippel-Landau gene loss-of-function mutations, and mid/high MetAP1/2 expression. Clinical investigation of MetAP2 inhibitor-based combinations in RCC is warranted.

More effective treatment modalities for head and neck squamous cell carcinoma (HNSCC) are urgently needed as globally 450,000 patients die of this disease annually. HNSCC was shown to express tissue factor (TF) making TF an interesting therapeutic target. Bakema and colleagues tested tisotumab vedotin (TV), an antibody-drug-conjugate directed to TF, in preclinical in vitro and in vivo models of HNSCC. TV killed HNSCC cell lines in vitro, and showed preclinical anti-tumor activity as monotherapy in xenograft models. In addition, TV also showed preclinical activity when combined with standard-of-care chemoradiotherapy. This work supports clinical exploration of tisotumab vedotin in HNSCC.

The tumor microenvironment (TME) plays a crucial role in the development and progression of malignant tumors. E7130 is a novel anticancer agent that ameliorates the tumor-promoting microenvironment and is currently undergoing Phase 1 clinical studies in advanced solid cancers. In this report, Ito, Yamaguchi, and their colleagues have examined preclinical tumor models using multimodal imaging of multiplex-IHC, dynamic contrast-enhanced (DCE)-MRI, and diffusion weighted (DW)-MRI as well as CyTOF analysis. They have identified a combination of MRI parameters and plasma biomarkers, such as TGF-β1 and collagen IV, which are non-invasive biomarkers of E7130 treatment response.