Cytotoxic protein hybrid and process for the preparation thereof

A process for preparing a cytotoxic protein hybrid expressed by the following formula (III-1) or (IV-1):

• Ab--(X.sub.2).sub.p --S.sub.1 --S.sub.2 --X.sub.4 --PAP).sub.n (III- 1)
• (Ab--(X.sub.2).sub.p --S.sub.1 --S.sub.2 --X.sub.4).sub.n PAP (IV-1)
• where Ab indicates an immunogloublin or its fragment;
• PAP is a protein which is obtained from Phytolacca americana and capable of inhibiting protein synthesis;
• n represents an integer of 1 to 3;
• X.sub.2 and X.sub.4 indicate a divalent organic group, respectively;
• S.sub.1 and S.sub.2 indicate a sulfur atom respectively;
• and p represents 0 or 1;
• comprising linking an immunoglobulin or its fragment, which has a thiol group either self-produced therein or introduced thereto, with a protein, which is obtained from Phytolacca americana, capable of inhibiting protein synthesis, and has a thiol group introduced thereto, by use of a cross-linking agent having two functional groups capable of reacting with thiol groups.

A process for preparing a cytotoxic protein hybrid expressed by the following formula (III-2) or (IV-2):

• Ab--(X.sub.2).sub.p --S.sub.1 --X.sub.3 --S.sub.2 --X.sub.4 --PAP).sub.n (III- 2)
• Ab--(X.sub.2).sub.p --S.sub.1 --X.sub.3 --S.sub.2 --X.sub.4).sub.n PAP (IV-2)
• wherein Ab indicates an immunogloublin or its fragment;
• PAP is a protein which is obtained from Phytolacca americana and capable of inhibiting protein synthesis;
• n represents an interger of 1 to 3;
• X.sub.2, X.sub.3 and X.sub.4 indicate a divalent organic group respectively;
• S.sub.1 and S.sub.2 indicate a sulfur atom respectively;
• and p is 0 or 1;
• comprising linking an immunoglobulin or its fragment, which has a thiol group either self-produced therein or introduced thereto, with a protein, which is obtained from Phytolacca americana, capable of inhibiting protein synthesis, and has a thiol group introduced thereto, by use of a crosslinking agent having two functional groups capable of reacting with thiol groups.

A process for preparing a cytotoxic protein hybrid expressed by the following formula (V) or (VI):

• ##STR20## where Ab indicates an immunoglobulin or its fragment;
• PAP is a protein which is obtained from Phytolacca americana and capable of inhibiting protein synthesis;
• X.sub.2 and X.sub.5 indicate a divalent group respectively;
• S.sub.1 indicates a sulfur atom;
• and p is 0 or 1;
• comprising reacting an immunoglobulin or its fragment having a thiol group either self-produced therein or introduced thereto with a protein which is obtained from Phytolacca americana, capable of inhibiting protein synthesis, and has a maleimide group introduced thereto.