Title:  Immunotherapy of tumor with monoclonal antibody against the 17-1A antigen

United States Patent:  6,444,207

Issued:  September 3, 2002

Inventors:  Schoemaker; Hubert J. P. (Devon, PA); Carrano; Richard A. (Phoenixville, PA)

Assignee:  Centocor, Inc. (Malvern, PA)

Appl. No.:  307044

Filed:  September 16, 1994

Disclosed is a method for treating a gastrointestinal tumor by administering a murine antibody which specifically binds an epitope of 17-1A antigen.

DETAILED DESCRIPTION OF THE INVENTION

This invention pertains to therapy of gastrointestinal tumors with repeated, high dose of murine antibody against the 17-1A antigen associated with most gastrointestinal tumors. This therapeutic approach is based upon several findings. Murine anti-17-1A antibody administered in multiple, high dose is generally well-tolerated by patients. The most common side effect is mild gastrointestinal symptoms. Allergic responses, however, do limit repeat therapy in some patients. In addition, although a human anti-murine antibody response is generally evoked by the murine antibody, the response does not drastically effect the pharmacokinetics of the administered murine antibody. This indicates that sequential, high doses of antibody can be given to achieve and maintain a continuous high plasma level of antibody. Maintaining a high circulating level of antibody optimizes transit of the antibody from intravascular space into the tumor, thereby enhancing access of the antibody to the tumor for more effective anti-tumor action. Further, sustained, high blood levels lead to a prolonged, higher concentration of antibody at the locus of action for more effective antibody dependent cell mediated cytolysis of the tumor cells.

According to the method of this invention, murine antibody against the 17-1A antigen is administered to patients afflicted with gastointestinal tumors in multiple doses of about 100 mg or more, preferably about 400 mg -1 gram, for a total dose of about 0.1 to 5 grams, preferably 1 to 5 grams. The antibody is administered parenterally preferably by intraveneous infusion. The antibody is generally administered suspended in a physiologically acceptable vehicle e.g. normal saline. The antibody doses can be given over intervals of 1-3 days to intervals of about a week. The dose regimen for an individual patient will depend, inter alia, on the patient's clinical status and on his ability to tolerate the dose without detrimental allergic or anaphylactic reaction. The objective is to provide antibody at fractional doses which yields a sustained, high plasma level of antibody over the course of therapy to provide increased access of the antibody to the tumor site.

Murine antibodies against 17-1A can be administered individually or in mixtures (cocktails) of two or more murine anti-17-1A antibodies. Preferably, anti-17-1A antibody having different epitopic specificity for 17-1A is employed in the combination in order to increase anti-tumor activity in an additive or synergistic fashion. Murine antibodies can be selected from the original 17-1A antibody or other murine antibodies which recognize similar or different epitopes of the 17-1A antigen, such as the M72, M74, M77 and M79 antibodies described below.

Murine antibody against 17-1A antigen can be used in passive immunotherapy of tumors of the gastrointestinal tract with which the 17-1A antigen is associated. Examples are gastrointestinal adenocarcinoma, colorectal carcinoma and pancreatic carcinoma. The murine antibody treatment can be adjuvant to other forms of therapy, including chemotherapy, radiotherapy and/or surgery. In particular, murine antibody therapy can be useful as adjuvant therapy directed against micro- or mini-metastases which are not amenable to surgical removal.

Claim 1 of 17 Claims

What is claimed is:

1. A method for treating a gastrointestinal tumor comprising administering to a patient afflicted with a gastrointestinal tumor, a murine monoclonal antibody which specifically binds to an epitope of 17-1A antigen, said antibody being administered in multiple doses of about 400 milligrams or more per dose.
 

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