Summary
A therapeutic trial using repeated doses of a mouse monoclonal antibody against the tumor-associated antigen (TAA) CO17-1A in metastatic colorectal carcinomas was carried out. Metastatic lesions sampled by repeated thick needle (1.2 mm) biopsies during therapy were examined immunohistochemically for the presence of various TAAs, mouse IgG, complement, and infiltrating leukocytes. The CO17-1A was consistently expressed in all cases along the basement membrane of tumor glands and could only be demonstrated on cryostat sections whereas the TAAs GICA19-9, GA73-3, and Br55-2 were also visualized in B5-fixed paraffin-embedded biopsies. The CO17-1A and GA73-3 were predominantly present at the basal region in contrast to the GICA 19-9 and Br55-2 which were predominant at the luminal and the apical region of the tumor glands. Antigenic modulation was not seen either after 24–72 h or during prolonged treatment. In all cases the infused mouse IgG was detected, from 24 h after infusion up to 6–8 weeks, mainly along the basal region of tumor glands. In 13/14 posttreatment biopsies, complement factor C3 was found at the same sites as mouse IgG. In 6 out of 9 posttreatment biopsies an increase in mononuclear cells (monocytes, natural killer (NK) cells and/or T cells) was observed. Monocytes were close to the tumor cells whereas NK cells and T cells were predominantly scattered in the stroma.
Similar content being viewed by others
References
Adams DO, Hall T, Steplewski Z, Koprowski H (1984) Tumors undergoing rejection induced by monoclonal antibodies of the IgG2a isotype contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis. Proc Natl Acad Sci 81:3506
Bedikian AY, Chen TT, Malahy MA, Patt YZ, Bodey GP (1984) Prognostic factors influencing survival of patients with advanced colorectal cancer: Hepatic artery infusion versus systemic intravenous chemotherapy for liver metastases. J Clin Oncol 2:174
Bergmark S, Hagfström LO (1969) The natural history of primary and secondary malignant tumors of the liver. I. The prognosis for patients with hepatic metastases from colonic and rectal carcinoma by laparotomy. Cancer 23:198
Dawson PM, Habib NA, Peck M, Blaxland JW, Luck RJ (1986) Patient survival with liver metastases from colorectal cancer — a district hospital experience. Eur J Surg Oncol 12:131
Douillard JY, Lehur PA, Vignoud J, Blottiere H, Maurel C, Thedrez P, Kremer M, Le Mevel B (1986) Monoclonal antibodies specific immunotherapy of gastro-intestinal tumors. Hybridoma 5 (suppl I):139
Dukes CE, Bussey HJR (1958) The spread of rectal cancer and its effects on prognosis. Br J Cancer 12:309
Ekberg H, Tranberg KG, Lundstedt C, Hahff G, Ranstam J, Jeppsson B, Bengmark S (1986) Determinants of survival after intraarterial infusion of 5-fluorouracil for liver metastases from colorectal cancer: A multivariate analysis. J Surg Oncol 31:246
Frödin JE, Biberfeld P, Christensson B, Philstedt P, Sundelius S, Sylvén M, Wahren B, Koprowski H, Mellstedt H (1986) Treatment of patients with metastasizing colo-rectal carcinoma with mouse monoclonal antibodies (MOAb17–1A). A progress report. Hybridoma 5 (suppl I):151
Garcia CF, Lowder J, Meeker TC, Bindl J, Levy R, Warnke RA (1985) Differences in “host infiltrates” among lymphoma patients treated with anti-idiotype antibodies: correlation with treatment response. J Immunol 135:4252
Goslin R, Steele Jr G, Zamcheck N, Mayer R, MacIntyre J (1982) Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum. Dis Colon Rectum 25:749
Herlyn DM, Koprowski H (1982) IgG2A monoclonal antibodies inhibit human tumor growth through interaction with effector cells. Proc Natl Acad Sci 79:4761
Herlyn DM, Herlyn MF, Steplewski Z, Koprowski H (1979) Monoclonal antibodies in cell-mediated cytotoxicity against human melanoma and colo-rectal carcinoma. Eur J Immunol 9:657
Herlyn DM, Herlyn MF, Ross AH, Ernst C, Atkinson B, Koprowski H (1984) Efficient selection of human tumor growth-inhibiting monoclonal antibodies. J Immunol Methods 73:157
Herlyn MF, Steplewski Z, Herlyn DM, Koprowski H (1986) CO17–1A and related monoclonal antibodies: Their production and characterization. Hybridoma 5 (suppl I):3
Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase Complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 29:577
Magnani JL, Nilson B, Brockhaus M, Zopf D, Steplewski Z, Koprowski H, Ginsburg V (1982) A monoclonal antibody defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II. J Biol Chem 257:14365
Mason DY, Bell JJ, Christensson B, Biberfeld P (1980) An immunohistological study of human lymphoma. Clin Exp Immunol 40:235
Mellstedt H, Frödin J-E, Christensson B, Shetye J, Biberfeld P, Lefvert A-K, Pihlstedt P, Sylvén M, Makower J, Wahren B, Ahlman B, Cedermark B, Erwald R, Klingenström P, Nathansson J, Rieger A, Koprowski H (1988) Application of monoclonal antibodies (MAb 17–1A) in the treatment of colorectal carcinomas: In: Carrano RA, Douillard JY (eds) Monoclonal antibodies in clinical oncology. Marcel Dekker, New York (in press)
Mellstedt H, Frödin J-E, Masucci G, Lindemalm C, Wedelin C, Christensson B, Shetye J, Biberfeld P, Lefvert A-K, Pihlstedt P, Makower J, Harmenberg U, Wahren B, Ahlman B, Cedermark B, Erwald R, Magnusson I, Nathansson J, Rieger A (1988) MAb 17–1A used for therapy of patients with metastatic colorectal carcinomas. In: Beger HG, Reisfeld R (eds) New approaches in cancer treatment. Springer-Verlag, Berlin (in press)
Neville AM, Gusterson BA (1985) Monoclonal antibodies and human tumors; pathological and clinical aspects. Eur J Cancer Clin Oncol 21:355
Porwit-Ksiazek A, Ksiazek T, Biberfeld P (1983) Leu-7+ (HNK-1+) cells. I. Selective compartmentalisation of Leu-7+ cells with different immunophenotypes in lymphatic tissues and blood. Scand J Immunol 18:485
Ross AH, Herlyn D, Diopoulos D, Koprowski H (1986) Isolation and characterization of a carcinoma-associated antigen. Biochem Biophys Res Commun 135:297
Schulz G, Staffileno LK, Reisfeld RA, Dennert G (1985) Eradication of established human melanoma tumor in nude mice by antibody-directed effector cells. J Exp Med 161:1315
Sears HF, Mattis J, Herlyn DM, Häyry P, Atkinson B, Ernst C, Steplewski Z, Koprowski H (1982) Phase I clinical trial of monoclonal antibody in treatment of gastro-intestinal tumors. Lancet I:762
Sears HF, Herlyn DM, Häyry P, Atkinson B, Ernst C, Steplewski Z, Koprowski H (1985) Phase II clinical trial of a murine monoclonal antibody cytotoxic for gastro-intestinal adenocarcinoma. Cancer Res 45:5910
Sears HF, Herlyn DM, Steplewski Z, Koprowski H (1986) Initial trial use of murine monoclonal antibodies as immunotherapeutic agents for gastro-intestinal adenocarcinoma. Hybridoma 5 (suppl I):109
Shen JW, Atkinson B, Koprowski H, Sears HF (1984) Binding of murine immunoglobulin to human tissues after immunotherapy with anti-colo-rectal carcinoma monoclonal antibody. Int J Cancer 33:465
Sindelar WF, Maher MM, Herlyn D, Sears HF, Steplewski Z, Koprowski H (1986) Trial of therapy with monoclonal antibody 17–1A in pancreatic carcinoma. Preliminary results. Hybridoma 5 (suppl I):125
Steplewski Z, Herlyn D, Lubeck M, Kimoto Y, Herlyn M, Koprowski H (1986) Mechanisms of tumor growth inhibition. Hybridoma 5 (suppl I):59
Tempero MA, Pour PM, Uchida E, Herlyn D, Steplewski Z (1986) Monoclonal antibody CO17–1A and leukapheresis in immunotherapy of pancreatic cancer. Hybridoma 5 (suppl I):133
Blaszczyk-Thurin M, Thurin J, Hindsgaul O, Karlsson KA, Steplewski Z, Koprowski H (1987) Y and blood group B type 2 glycolipid antigens accumulate in a human gastric carcinoma cell line as detected by monoclonal antibody: Isolation and characterization by mass spectrometry and NMR spectroscopy. J Biol Chem 262(1):372
Verrill H, Goldberg M, Rosenbaum R, Abbott R, Simunovic L, Steplewski Z, Koprowski H (1986) Clinical trial of Wistar Institute 17–1A monoclonal antibody in patients with advanced gastro-intestinal adenocarcinoma. A preliminary report. Hybridoma 5 (suppl I):175
Author information
Authors and Affiliations
Additional information
This study was supported by grants from the Cancer Society in Stockholm, the King Gustav Vth Jubilee Fund, The Swedish Cancer Society and the Karolinska Institute Foundations
Rights and permissions
About this article
Cite this article
Shetye, J., Frödin, JE., Christensson, B. et al. Immunohistochemical monitoring of metastatic colorectal carcinoma in patients treated with monoclonal antibodies (MAb 17-1A). Cancer Immunol Immunother 27, 154–162 (1988). https://doi.org/10.1007/BF00200021
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00200021