The application discloses a high-safety tumor treatment preparation based on a
prodrug-
enzyme-
neutralizing antibody three-
system, and a preparation method and application thereof. The preparation comprises three core components: (a) a
prodrug, which is coupled by an anti-tumor
drug (such as
doxorubicin) and
cephalosporin; (b) an activating
enzyme, such as beta-lactamase, which is specifically expressed in the tumor by phage, catalyzes the
hydrolysis of the
prodrug, and releases the active
drug; and (c) a
neutralizing antibody, such as an anti-
doxorubicin monoclonal antibody, which can specifically bind and neutralize the active
drug overflowing into the
blood circulation. The application first integrates the precise killing strategy of "prodrug-local activation" and the safety strategy of "
neutralizing antibody-systematic protection" into a complete treatment
closed loop, utilizes the "differential
neutralization" characteristics of the anti-
doxorubicin antibody, effectively protects normal tissues from toxic damage under the premise of not affecting the local
efficacy of the tumor, and significantly improves the
therapeutic index of the
chemotherapy drug, reduces the side effects such as
cardiotoxicity and
bone marrow suppression, and provides a new paradigm with high efficiency and safety for tumor treatment.