Cancer

In vitro and mouse studies suggest a cell-penetrating antibody targeting activated KRAS could help treat KRAS-mutant cancers. In a panel of KRAS-mutant human cancer cell lines, a cell-penetrating IgG1 antibody against KRAS, modified with N-terminal peptide that binds tumor-associated integrins α_vβ₃ and α_vβ₅ (RT11-i), decreased proliferation compared with a control cell-penetrating antibody lacking the N-terminal peptide. In xenograft mouse models of colorectal cancer and fibrosarcoma, RT11-i decreased growth of oncogenic KRAS-mutant tumors compared with the control antibody or vehicle, whereas RT11-i did not decrease growth of wild-type KRAS tumors. In the colorectal cancer model, RT11-i plus Erbitux cetuximab decreased tumor growth and increased survival compared with Erbitux alone or Erbitux plus the control antibody. Ongoing work by Orum Therapeutics Inc. includes optimizing RT11-i to identify development candidates and developing variants that bind different tumor cell types.

Eli Lilly and Co. and Merck KGaA market Erbitux, a mAb against epidermal growth factor receptor (EGFR; ErbB1; HER1), to treat colorectal cancer and head and neck cancer...