Immunomodulatory properties of anticancer monoclonal antibodies: is the 'magic bullet' still a reliable paradigm?

摘要: HER2/neu, VEGF and CD20 have shown significant antitumor activity [3,4]. On the basis of this, when these hypothetic magic bullets were exploited in clinical translation, any potential issue concerning their immunological nature or interference with host microenvironment has been considered superfluous and, consequently, poorly investigated. Recently, research agents addressed owing to identification further biochemical targets critical for tumor cell growth survival eventually, synergistic i nteraction c onventional a nticancer cytotoxic drugs. At present, there is no direct evidence demonstrating that majority mAbs used practice related inhibition specific target transducers. In addition, many cases, not even clear demonstration expression mAb on cancer cells area predictive response treatment (i.e., EGFR cetuximab/panitumumab, VEGF/VEGF receptor bevacizumab) [5]. Furthermore, it use alternative small molecules ability inhibit same pharmaco logical as (e.g., erlotinib place cetuximab colon cancer) provide much stronger vitro does produce anticancer effect setting [6]. Many hypotheses theories formulated support current vision activity; however, molecular inhibitors, accordance bullet paradigm, simply be scientific dogma. Clear examples are represented by raised against families, such panitumumab, which recognize EGFR-1, There an exponential increase development monoclonal antibodies (mAbs) other target-specific drugs human over last 15 years. The encouraging results obtained from large trials refashioned ‘magic bullet’ paradigm. Ehrlich hypothesized possibility using killing darts discriminate normal counterparts. This paradigm conceptual conventional chemotherapy, selective tissue therefore, associated toxicity [1,2].