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Experimental immunotherapy of colorectal carcinoma by monoclonal antibody ND4
Timothy M Kelly1, Peter Thomas, Aniruddha Ganguly
1Department of Surgery, Laboratory of Cancer Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
The potential for experimental immunotherapy of colorectal cancers by mouse IgG2a monoclonal antibody (MAb) ND4 is investigated. The MAb ND4 recognizes a 160 kd cell surface glycoprotein that is strongly expressed in 58% of colorectal carcinomas. The antibody is internalizable by MIP-101 colorectal carcinoma cells. Biodistribution studies in nude mice bearing MIP-101 subcutaneous tumors showed accumulation of 125I-ND4 MAb in tumors from 5% at 18 hours to 14% of the injected dose per gram tissue at 14 days after intraperitoneal (i.p.) injection. Experimental immunotherapy studies using 125I-ND4 in MIP-101 tumor-bearing nude mice showed 64% inhibition of tumor growth 2 weeks after two i.p. injections at 7-day intervals. The MAb ND4 may be useful as a therapeutic reagent for colorectal tumors.
Insights
Mouse monoclonal antibody ND4 shows potential for colorectal cancer immunotherapy. This antibody targets a glycoprotein on cancer cells, inhibiting tumor growth by 64% in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Biology
Background:
- Colorectal cancer remains a significant health concern with limited targeted therapies.
- Monoclonal antibodies (MAbs) offer a promising avenue for targeted cancer treatment.
- Identifying specific tumor-associated antigens is crucial for developing effective MAb-based immunotherapies.
Purpose of the Study:
- To investigate the therapeutic potential of mouse IgG2a monoclonal antibody (MAb) ND4 for experimental immunotherapy of colorectal cancers.
- To characterize the target antigen recognized by MAb ND4 and its expression in colorectal carcinomas.
- To evaluate the biodistribution and anti-tumor efficacy of MAb ND4 in preclinical models.
Main Methods:
- Characterization of MAb ND4 binding to a 160 kd cell surface glycoprotein.
- Assessment of MAb ND4 internalization by MIP-101 colorectal carcinoma cells.
- Biodistribution studies of 125I-labeled MAb ND4 in nude mice bearing MIP-101 tumors.
- Evaluation of tumor growth inhibition following MAb ND4 immunotherapy in vivo.
Main Results:
- MAb ND4 recognizes a 160 kd glycoprotein strongly expressed in 58% of colorectal carcinomas.
- The antibody is internalizable by MIP-101 colorectal carcinoma cells.
- Biodistribution studies showed significant accumulation of 125I-ND4 MAb in tumors.
- Immunotherapy studies demonstrated a 64% inhibition of tumor growth in treated mice.
Conclusions:
- MAb ND4 targets a relevant antigen on colorectal cancer cells.
- The antibody exhibits favorable biodistribution and significant anti-tumor activity in preclinical models.
- MAb ND4 holds potential as a therapeutic reagent for colorectal tumors.
