Monoclonal antibodies (MoAbs) show promise as a prognostic as
well as therapeutic tool in some minimal residual cancers, said
Gert Riethmüller, MD, of the University of Munich's Institute
Speaking at a symposium sponsored by the Cancer Research Institute,
Dr. Riethmüller reported that an ongoing trial is using MoAbs
to detect cytokeratin-positive cells in bone marrow as evidence
of micrometastatic disease in patients with early cancers of the
lung, breast, gastrointestinal tract, and urogenital system. A
therapeutic trial with the 17-1A MoAb is also underway.
Acknowledging that primary prevention of cancer is still beyond
reach, Dr. Riethmüller characterized the avoidance of metastatic
disease as "secondary prevention," and called it a realistic
goal. He pointed out that the systematic dissemination of tumor
cells occurs early in many epithelial tumor types. Thus, the key
to secondary prevention is the identification and treatment of
minimal residual disease before it manifests clinically.
Dr. Riethmüller said that cytokeratin expression is not a
tumor-specific characteristic; rather, it is ubiquitous in normal
epithelial tissues. Nonetheless, the origin and malignant nature
of the targeted cells in the bone marrow can be established through
evidence of differentiation antigens and mutated oncogene proteins
expressed by the tumor cells.
This method has been employed successfully in early cancers of
the lung, breast, and large bowel, and clinical follow-up studies
have confirmed the prognostic significance of cytokeratin-expressing
cells as a marker for occult metastatic disease, he said.
Once identified, these micrometastases can be targeted for immunotherapy.
Because the cells are located in the mesenchymal interstitia,
they are accessible to IV injection of antibodies and secondary
effector cells and molecules.
In a randomized prospective trial in which patients with colorectal
cancer (Dukes stages C1 and C2) were treated with the 17-1A MoAb
within 2 weeks of complete resection, the treated group showed
an improved 7-year survival over the untreated group, Dr. Riethmüller
The therapeutic effect was most pronounced on manifestation of
distant metastases, he said, whereas no effect was seen on local
relapses. Toxic effects were minor, consisting of diarrhea of
short duration in a few patients.
A new phase I/II trial is planned using chimerized MoABs to reduce
the risk of rejection from repeated treatments, Dr. Riethmüller
said. He noted that ongoing research into other antigen targets
may make possible a multipronged approach, employing a defined
combination of different antibodies in "preemptive strike"