Abstract
Tumor metastasis is generally agreed to be the major cause of cancer death. Over the last few years, studies of new diagnosis techniques and tumor immunotherapy have made great progress. Recent clinical studies on the occult metastases of breast, lung and colorectal cancer all suggested that the detection of micrometastases in bone marrow is prognostically important and provides substantial evidence of tumor dissemination. On the other hand, two kinds of the mAb-based immunotherapy have been approved for the treatment against epithelial cancer. Monoclonal antibody (mAb) 17-1A for colorectal carcinomas and mAb herceptin for breast cancer both have produced good curative effects. Potential therapeutics based on some antibodies with prominent antitumor activity also has shown obvious clinical effect. These studies indicate that detection of micrometastasis in circulatory system and immunotherapy by eliminating metastatic malignant cells suggested a new strategy against the metastatic cancer.
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Henderson, B. E., Ross, R. K., Pike, M. C., Toward the primary prevention of cancer, Science, 1991, 254: 1131.
Mou, D. C., Cai, S. L., Peng, J. R. et al., Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells, British Journal of Cancer, 2002, 86, 110.
Oberneder, R., Riesenberg, R., Kriegmair, M. et al., Immunocytochemical detection and phenotypic characterization of micrometastatic tumour cells in bone marrow of patients with prostate cancer, Urol. Res., 1994, 22: 3.
Cote, R. J., Beattie, E. J., Chaiwun, B. et al., Detection of occult bone marrow metastases in patients with operable lung carcinoma, Ann. Surg., 1995, 222: 415.
Pantel, K., Isbicki, J., Passlick, B. et al., Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small cell lung cancer without overt metastases, Lancet, 1996, 347: 649.
Lindemann, F., Schlimok, G., Dirschedl, P. et al., Prognostic significance of micrometastatic tumor cells in bone marrow of colorectal cancer patients, Lancet, 1992, 340: 685.
Kasper, M., Stosiek, P., Typlt, H. et al., Histological evaluation of three new monoclonal anti-cytokeratin antibodies, Eur. J. Cancer Clin. Oncol., 1987, 23(2): 137.
Butschak, G., Neupert, G., Karsten, U., Patterns of cytokeratins and lamins in rat liver and in rat livercell lines as shown by immunoblotting using the monoclonal antibodies A45-B/B3 and A51-B/H4, Acta Histochem., 1992, 16: 107.
Chen, Y. H., Gao, W. H., Li, J. et al., Detection of bone marrow micrometastasis, Hybridoma, 1999, 18(5): 465.
Gross, H. J., Verwer, B., Houck, D. et al., Model study detecting breast cancer cells in peripheral blood mononuclear cells at frequencies as low as 10(-7), Proc. Natl. Acad. Sci. USA, 1995, 92(2): 537.
Nishizaki, T., de Vries, S., Chew, K. et al., Genetic alterations in primary breast cancers and their metastases: direct comparison using modified comparative genomic hybridization, Genes Chromosomes Cancer, 1997, 19(4): 267.
Aragane, H., Sakakura, C., Nakanishi, M. et al., Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization, Int. J. Cancer, 2001, 94(5): 623.
Braun, S., Hepp, F., Kentenich, C. R. M. et al., Monoclonal antibody therapy with edrecolomab in breast cancer patients: monitoring of elimination of disseminated cytokeratin-positive tumor cells in bone marrow, Clin. Cancer Res., 1999, 5: 3999.
Mangel, J., Buckstein, R., Imrie, K. et al., Immunotherapy with rituximab following high-dose therapy and stem-cell transplantation for mantle cell lymphoma, Semin. Oncol., 2002, 29 (Suppl. 2): 56.
Maletz, K., Kufer, P., Mack, M. et al., Bispecific single-chain antibodies as effective tools for eliminating epithelial cancer cells from human stem cell preparations by redirected cell cytotoxicity, Int. J. Cancer, 2001, 93(3): 409.
Wood, D. P. J., Banks, E. R., Humphreys, S., Rangnekar, V. M., Sensitivity of immunohistochemistry and polymerase chain reaction in detecting prostate cancer cells in the bone marrow, J. Histochem. Cytochem., 1994, 42: 505.
Pajonk, F., Schlessmann, S., Guttenberger, R., Henke, M., Epithelial cells in the peripheral blood of patients with cancer of the head and neck: incidence, detection and possible clinical significance, Radiotherapy and Oncology, 2001, 59: 213.
Aerts, J., Wynendaele, W., Paridaens, R. et al., A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect breast carcinoma cells in peripheral blood, Ann Oncol., 2001, 12(1): 39.
Gelmini, S., Tricarico, C., Vona, G. et al., Real-Time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for the measurement of prostate-specific antigen mRNA in the peripheral blood of patients with prostate carcinoma using the taqman detection system, Clin. Chem. Lab Med., 2001, 39(5): 385.
Yuan, A., Yu, C. J., Luh, K. T. et al., Quantification of VEGF mRNA expression in non-small cell lung cancer using a real-time quantitative reverse transcription-PCR assay and a comparison with quantitative competitive reverse transcription-PCR, Lab Invest., 2000, 80(11): 1671.
Rosenberg, S. A., Progress in human tumor immunology and immunotherapy, Nature, 2001, 411(17): 380.
Rosenberg, S. A., Lotze, M. T., Muul, L. M. et al., A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2, or high dose interleukin-2 alone, N. E. J. M., 1987, 316: 889.
Freedman, R. S., Edwards, C. L., Kavavanagh, J. J. et al., Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumourinfiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial, J. Immunother., 1994, 16: 198.
Thiounn, N., Mathiot, C., Flam, T. et al., CD4 TIL induce complete response in patients treated with IL-2 (interleukin-2), Preliminary study (in French), J. Urol., 1994, 100: 185.
Kruit, W. H., Goey, S. H., Lamers, C. H. et al., High-dose regimen of interleukin-2 and interferon-alpha in combination with lymphokine-activated killer cells in patients with metastatic renal cell cancer, J. Immunother., 1997, 20(4): 312.
Rosenberg, S. A., Yannelli, J. R., Yang, J. C. et al., Treatment of patients with metastatic melanoma with autologous tumorinfiltration lymphocytes and interleukin-2, J. Natl. Cancer Inst. USA, 1994, 86: 1159.
Maxwell-Armstrong, C. A., Durrant, L. G., Buckley, T. J. D. et al., Randomized double-blind phase II survival study comparing immunization with the anti idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer, British Journal of Cancer, 2001, 84(11): 1443.
Hui, J. Y., Li, G. D., Kong, Y. Y., Wang, Y., DNA-based immunization against hepatitis B surface antigen carrying preS epitopes, Chinese Science Bulletin, 1999, 44(7): 620.
Goydos, J. S., Elder, E., Whiteside, T. L. et al., A phase I trial of a synthetic mucin peptide vaccine induction of specific immune reactivity in patients with adenocarcinoma, Journal of Surgical Research, 1996, 63(1): 298.
Jager, E., Hohn, H., Necker, A. et al., Peptide-specific CD8+T-cell evolution in vivo: response to peptide vaccination with Melan-A/MART-I, International Journal of Cancer, 2002, 98(3): 376.
Caudill, M. M., Li, Z. H., HSPPC-96: a personalised cancer vaccine, Expert Opinion on Biological Therapy, 2001, 1(3): 539.
Sahin, U., Tureci, O., Pfreundschuh, M., Serological identification of human tumor antigens, Curr. Opin. Immunol., 1997, 9: 709.
Chen, Y. T., Old, L. J., Cancer-testis antigens: targets for cancer immunotherapy, Cancer J. Sci. Am., 1999, 5: 16.
Old, L. J., Chen, Y. T., New paths in human cancer serology, J. Exp.Med., 1998, 187: 1163.
Lee, L., Wang, R. F., Wang, X. et al., NY-ESO-1 may be a potential target for lung cancer immunotherapy, Cancer J. Sci. Am., 1999, 5(1): 20.
Chen, Y. T., Scanlan, M. J., Sahin, U. et al., A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening, Proc. Natl. Acad. Sci. USA, 1997, 94: 1914.
Mackensen, A., Herbst, B., Chen, J. L. et al., Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells, Int. J. Cancer, 2000, 86(3): 385.
Nestle, F. O., Alijagic, S., Gilliet, M. et al., Vaccination of melanoma patients with peptideor tumor lysate-pulsed dendritic cells, Nat. Med., 1998, 4: 328.
Boon, T., van der Bruggen, P., Human tumor antigens recognized by T lymphocytes, J. Exp. Med., 1996, 183: 725.
Rosenberg, S. A., Kawakami, Y., Robbins, P. F. et al., Identification of the genes encoding cancer antigens: implications for cancer immunotherapy, Adv. Cancer Res., 1996, 70: 145.
Pardoll, D. M., Topalian, S. L., The role of CD4+T-cell responses in antitumor immunity, Curr. Op. Immunol., 1998, 10: 588.
Litvinov, S. V., Velders, M. P., Bakker, H. A. M. et al., Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule, J. Cell Biol., 1994, 125: 437.
Bumol, T. F., Marder, P., de Herdt, S. J. et al., Characterization of the human tumor and normal tissue reactivity of the KS1/4 monoclonal antibody, Hybridoma, 1988, 7: 407.
Gottlinger, H., Johnson, J., Riethmuller, G., Biochemical and epitope analysis of the 17-1A membrane antigen, Hybridoma, 1986, 5(Suppl. 1): S29.
Adkins, J. C., Spencer, C. M., Edrecolomab (Monoclonal Antibody 17-1A), Drugs, 1998, 56(4): 619.
Riethmuller, G., Schneider-Gadicke, E., Schlimok, G. et al., Randomized trial of monoclonal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoman, Lancet, 1994, 343: 1177.
Riethmuller, G., Holz, E., Schlimok, G. et al., Monoclonal antibody therapy for resected Dukes’ C colorectal cancer: seven-year outcome of a multicenter randomized trial, J. Clin. Oncol., 1998, 16(5): 1788.
Ranghammer, P., Frodin, J. E., Hjelm, A. L. et al., Different dose regimens of the mouse monoclonal antibody 17-1A for therapy of patients with metastatic colorectal carcinoma, Int. J. Oncol., 1995, 7: 1049.
Sindelar, W. F., Maher, M. M., Herlyn, D. et al., Trial of therapy with monoclonal antibody 17-1A in pancreatic carcinoma: preliminary results, Hybridoma, 1986, 5(Suppl. 1): S125.
Jain, R. K., Delivery of molecular medicine to solid tumors, Science, 1996, 27: 1079.
Hempel, D., Muller, P., Oruzio, D. et al., Combination of high-dose chemotherapy and monoclonal antibody in breast-cancer patients: a pilot trial to monitor treatment effects on disseminated tumor cells, Cytotherapy, 2000, 2(4): 287.
Weiner, L. M., Adams, G. P., New approaches to antibody therapy, Oncogene, 2000, 19(53): 6144.
Dillman, R. O., Perceptions of Herceptin: a monoclonal antibody for the treatment of breast cancer, Cancer Biother. Radiopharm., 1999, 14(1): 5.
Baselga, J., Clinical trials of Herceptin(R) (trastuzumab), Eur. J. Cancer, 2001, 37(Suppl. 1): 18.
Agus, D. B., Bunn, P. A. Jr., Franklin, W. et al., HER-2/neu as a therapeutic target in non-small cell lung cancer, prostate cancer, and ovarian cancer, Semin. Oncol., 2000, 27(Suppl. 11): 53.
Zhang, S., Zhang, H. S., Cordon-Cardo, C. et al., Selection of tumor antigens as targets for immune attack using immunohistochemistry: II. blood group-related antigens, Int. J. Cancer, 1997, 73: 50.
Trail, P. A., Wiliner, D., Lasch, S. J. et al., Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates, Science, 1993, 261: 212.
Sjögren, H. O., Isaksson, M., Willner, D. et al., Antitumor activity of carcinoma-reactive BR96-doxorubicin conjugate against human carcinomas in athymic mice and rats and syngeneic rat carcinomas in immunocompetent rats, Cancer Res., 1997, 57: 4530.
Tolcher, A. W., Sugarman, S., Gelmon, K. A. et al., Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer, J. Clin. Oncol., 1999, 17: 478.
Schlimok, G., Pantel, K., Loibner, H. et al., Reduction of metastatic carcinoma cells in bone marrow by intravenously administered monoclonal antibody: towards a novel surrogate test to monitor adjuvant therapies of solid tumours, Eur. J. Cancer, 1995, 31: 1799.
Cott, A. M., Geleick, D., Rubira, M. et al., Construction, production, and characterization of humanized anti-Lewis Y monoclonal antibody 3S193 for targeted immunotherapy of solid tumors, Cancer Res., 2000, 60(12): 3254.
Maletz, K., Kufer, P., Mack, M. et al., Bispecific single-chain antibodies as effective tools for eliminating epithelial cancer cells from human stem cell preparations by redirected cell cytotoxicity, Int. J. Cancer, 2001, 93(3): 409.
McLaughlin, P., Grillo-Lopez, A. J., Link, B. K. et al., Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program, Journal of Clinical Oncology, 1998, 16: 2825.
Verschuuren, E. A. M., Stevens, S. J. C., Van Imhoff, G. W. et al., Treatment of posttransplant lymphoproliferatieve disease with rituximab: The remission, the relapse, and the complication, Transplantation, 2002, 73(1): 100.
Zaja, F., Iacona, I., Masolini, P. et al., B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia, Haematologica, 2002, 87(2): 189.
Saffran, D. C., Raitano, A. B., Hubert, R. S. et al., Anti-PSCA mAbs inhibit tumor growth and metastasis formation and prolong the survival of mice bearing human prostate cancer xenografts, Proc. Natl. Acad. Sci. USA, 2001, 98(5): 2658.
Maguire, H. C. Jr., Berd, D., Lattime, E. C. et al., Phase I study of R24 in patients with metastatic melanoma including evaluation of immunologic parameters, Cancer Biother. Radiopharm., 1998, 13(1): 13.
Braun, S., Hepp, F., Sommer, H. L., Pantel, K., Tumor-antigen heterogeneity of disseminated breast cancer cells: Implications for immunotherapy of minimal residual disease, Int. J. Cancer, 1999, 84: 1.
Meredith, R. F., Khazaeli, M. B., Plott, W. E. et al., Initial clinical-evaluation of iodine-125-labeled chimeric 17-1a for metastatic colon-cancer, Journal of Nuclear Medicine, 1995, 36(12): 2229.
Shetye, J., Ragnhammar, P., Liljefors, M. et al., Immunopathology of metastases in patients of colorectal carcinoma treated with monoclonal antibody 17-1A and granulocyte macrophage colony-stimulating factor, Clinical Cancer Research, 1998, 4(8): 1921.
Flieger, D., Spengler, U., Beier, I. et al., Augmentation of 17-1A-induced antibody-dependent cellular cytotoxicity by the triple cytokine combination of interferon-alpha, interleukin-2, and interleukin-12, Journal of Immunotherapy, 2000, 23(4): 480.
Lance, A. L., An attractive force in metastasis, Nature, 2001, 410: 24.
Muller, A., Homey, B., Soto, H. et al., Involvement of chemokine receptors in breast cancer metastasis, Nature, 2001, 410: 50.
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Qin, L., Xiao, Y. & Chen, Y. Strategy against micrometastasis of epithelial cancer: Detection and elimination. Chin.Sci.Bull. 47, 1415–1421 (2002). https://doi.org/10.1360/02tb9312
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DOI: https://doi.org/10.1360/02tb9312