Immunodiagnosis and immunotherapy of isolated tumor cells disseminated to bone marrow of patients with colorectal cancer.
Micrometastatic spread of viable carcinoma cells is thought to be the leading cause of death in patients with completely resectable colorectal cancer. Since this minimal spread is missed by current tumor staging procedures, immunocytochemistry with monoclonal antibodies to epithelial cytokeratins have been successfully applied to detect individual carcinoma cells disseminated to mesenchymal organs such as bone marrow. Although the skeleton is not a preferential site of overt metastases in colon cancer, individual cytokeratin-positive tumor cells in bone marrow can be detected in about 30% of patients with no clinical signs of overt metastases (stage MO). The presence of these cells in bone marrow at the time of primary surgery turned out to be a strong independent indicator for subsequent relapse in organs such as liver and lungs. In a randomized, multicenter trial it could be furthermore demonstrated that the intravenous administration of the monoclonal antibody 17-1A into patients with Dukes C colon cancer significantly reduced the overall death rate by 30% and decreased the recurrence rate by 27%, thus underscoring the accessibility of micrometastatic tumor cells for immunotherapy. The present article reviews the current state of immunologic strategies used to detect, characterize, and treat minimal residual colon cancer.
Braun
S
S
I. Universitats-Frauenklinik, Ludwig-Maximilians-Universitat, Munchen, Germany.
Pantel
K
K
D000704:Analysis of Variance; D019046:Bone Marrow Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D007633:Keratins