This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Durrant, L. G. Articles by Robins, R. A. Search for Related Content PubMed PubMed Citation Articles by Durrant, L. G. Articles by Robins, R. A.

Enhanced Cell-mediated Tumor Killing in Patients Immunized with Human Monoclonal Antiidiotypic Antibody 105AD7¹

Departments of Surgery [L. G. D., T. J. D. B., G. W. L. D., J. D. H.] and Immunology [H. F. S., R. A. R.], University of Nottingham, Nottingham NG7 2 RD, United Kingdom

A human antiidiotypic monoclonal antibody (105AD7) has been shown to induce antitumor cellular responses in animals and appears to prolong survival in patients with metastatic colorectal cancer without associated toxicity. Proliferative leukocyte responses to the targeted tumor antigen gp72 were observed in these patients and plasma interleukin 2 levels were increased following immunization. Autologous tumor tissue was not available in these patients, so antitumor cytotoxicity could not be measured. This issue has now been addressed in an adjuvant clinical study in primary rectal cancer patients.

Six patients with rectal cancer were immunized preoperatively with 105AD7. Peripheral blood lymphocytes taken prior to immunization were tested against tumor cells extracted from biopsies also obtained prior to immunization or from natural killer (NK)-sensitive target cells. Cryopreserved lymphocytes taken before and after tumor immunization, fresh peripheral blood lymphocytes taken immediately prior to surgery, and lymphocytes from tumor-draining lymph nodes were tested against autologous cells from the resected specimen or NK-sensitive target cells. Significant killing of autologous tumor cells, which was not due to NK activity, was seen with cryopreserved lymphocytes or lymph node cells of three patients at 1–2 weeks postimmunization with 105AD7 but not on pretreatment biopsies. Enhanced NK activity was seen 2–3 weeks postimmunization in 3 of 6 patients. These results indicate that 105AD7 human monoclonal antibody immunization enhances cytotoxicity in rectal cancer patients by specific and nonspecific effector mechanisms.

¹ This work was supported by Cancer Research Campaign Grants SP2167/0101 and SP1886/0403.

² To whom requests for reprints should be addressed.

Received 6/27/94. Accepted 8/ 1/94.

This article has been cited by other articles:

				J. L. Murray, M. Gillogly, K. Kawano, C. L. Efferson, J. E. Lee, M. Ross, X. Wang, S. Ferrone, and C. G. Ioannides Fine Specificity of High Molecular Weight-Melanoma-Associated Antigen-Specific Cytotoxic T Lymphocytes Elicited by Anti-Idiotypic Monoclonal Antibodies in Patients with Melanoma Cancer Res., August 1, 2004; 64(15): 5481 - 5488. [Abstract] [Full Text] [PDF]

				M. Alfonso, A. Diaz, A. M. Hernandez, A. Perez, E. Rodriguez, R. Bitton, R. Perez, and A. M. Vazquez An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients J. Immunol., March 1, 2002; 168(5): 2523 - 2529. [Abstract] [Full Text] [PDF]

				C A Maxwell-Armstrong, L G Durrant, R A Robins, A M Galvin, J H Scholefield, and J D Hardcastle Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7 Gut, October 1, 1999; 45(4): 593 - 598. [Abstract] [Full Text] [PDF]

				I. Spendlove, L. Li, J. Carmichael, and L. G. Durrant Decay Accelerating Factor (CD55): A Target for Cancer Vaccines? Cancer Res., May 1, 1999; 59(10): 2282 - 2286. [Abstract] [Full Text] [PDF]

				K. A. Foon, J. Yannelli, and M. Bhattacharya-Chatterjee Colorectal Cancer as a Model for Immunotherapy Clin. Cancer Res., February 1, 1999; 5(2): 225 - 236. [Full Text] [PDF]