β-Diketone modified trastuzumab: A next-generation of Herceptin for resistant breast cancer cells?

Abstract: Despite the initial efficacy of trastuzumab (commercially named Herceptin), acquired resistance in a majority of patients remains the biggest hurdle in breast cancer therapy. Recently, the Scripps Research Institute developed a method termed “instant immunity”, in which antibodies (chemical programmed antibody) are rapidly induced by chemicals like β-diketone. When β-diketone is chemically linked to peptides specifically targeting cancer cells, the instant chemical programmed antibody would clear the cancer cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-directed cytotoxicity (CDC). This novel strategy has a super advantage over passive immunization or immunization with recombinant or vectored vaccines because it induces a universal immune response and memory. Theoretically, combination of the cancer cell specific recognition advantage of trastuzumab and cancerous cell clearance of active immunization would be an option for trastuzumab resistant patients, which harbors both the advantages of cancer specific targeting of trastuzumab and active immunization of the “instant immunity”, implicating a better clinical outcome. Further studies are needed to verify our hypothesis, which is worth validating. [Copyright &y& Elsevier]