Experimental tumoricidal effects of monoclonal antibody against solid breast tumors.

Abstract

Two distinct monoclonal antibodies (mAbs) were effective in the therapy of breast carcinomas of human origin established and growing in nude mice. Passive administration of either of the antibodies produced very rapid (less than 1 week) and significant reduction of in vivo tumor volume. Each of the mAbs showed in vivo targeting of the tumors. Histological analysis of mAb-treated tumors revealed extensive cellular necrosis. Each of the antibodies in vitro was effective in complement-mediated cytolysis at a concentration <1 ng/ml. The tumoricidal responses show that this is a useful model for passive human immunotherapy using mAbs.The treatment of malignant tumors with heteroantisera has been investigated for many years with interesting but inconclusive results (1). Hybridoma technology has provided monoclonal antibody (mAb) reagents, which may circumvent difficulties associated with the use of heteroantisera (2). Tumor-associated mAbs have been developed in the last few years by many workers, and some have investigated therapeutic efficacy in both animal and human subjects (3-5). Investigators have reported on the ability of mAbs to inhibit tumor growth by the administration of a mAb concurrent with or within several days of the implantation of tumor cells (6,7). However, passive mAb therapy has not been reported to decrease the volume of well established progressively growing solid tumors.Recently, mAbs developed in this laboratory against breast cancer cells have been shown to bind the target cells with high specificity (8). Passive immunotherapy experiments were performed to assess the therapeutic potential of these reagents. MATERIALS AND METHODSAnimals. Four-to six-week-old female Swiss nude (nu/nu) athymic mice were obtained from Sprague-Dawley. The mice were maintained in a laminar-flow apparatus under pathogenlimited conditions. Cells. Human breast carcinomas (BT-20, MCF-7, and MDA-MB-157) were obtained from the Breast Cancer Task Force, National Cancer Institute (9-11). Other human nonmammary tumor cells used were obtained from staff at Roswell Park Memorial Institute. MOLT 4 (T-cell leukemia), (B-cell leukemia), Peer (T-cell leukemia), and U-937 (erythroleukemia) were obtained from J. Minowada; K-562 (monocytoid leukemia), from J. Pauly; Chago (lung carcinoma), from B. Schepart; Daudi (Burkitt's lymphoma) and Palarmo (melanoma), from S. Leong and J. Horoszewicz; and AsPC-1 (pancreas carcinoma), from M. Tan. CCRF/SB (B-cell leukemia) and CCRF/ CEM (T-cell leukemia) were obtained from the American Type Culture Collection.All cell lines were maintained in vitro in RPMI 1640 medium/10% fetal calf serum supplemented with glutamine/pyruvate/nonessential amino acids/insulin. Cultures were maintained at 370C in humidified 5% C02/95% air.Tumors. Cells were scraped, washed, and resuspended in RPMI 1640 medium. Tumor-cell viability was assessed by trypan blue dye exclusion, and only cell suspensions of >95% viability were used. The nude mice were injected with 5-10 x 106 cells subcutaneously on their dor...

K562 erythroleukemic cells are equipped with multiple mechanisms of resistance to lysis by complement

“…Complement activation can be targeted to neoplastic tissues by either naturally occurring anti-tumor antibodies 3,22,23 or by therapeutic administration of MAb to tumor-associated antigens (TAA). 24,25 Malignant cells, however, are resistant to some extent to complement-mediated lysis.…”

“…1,2 Anti-tumor effects of mouse monoclonal antibodies (MAb) directed against human tumor cells growing in nude mice have been shown to be mediated through complement activation. 3,4 The efficiency of complement-mediated tumor cell lysis, however, seems to be hampered by several protective mechanisms employed by the tumor cells. Nucleated cells, in general, use multiple strategies to resist complement attack.…”

Role of the Kidney in Metabolic Change of Interleukin-2

“…A purified protein (monoclonal antibody F36/22) was labeled with l25I [15] and incubated with the kidney homogenate under the identical conditions as those of 125I-IL-2, i.e. pH 4 for 3 h at 37 °C.…”

Immunotherapy in a spontaneously developed murine mammary carcinoma with syngeneic monoclonal antibody

“…We have previously reported the effective in vivo use of two murine monoclonal antibodies (McAbs, F36/22 IgG3, M7/102 IgG2a) in radiolocalization of tumor and induction of significant tumor regression of progressively growing human breast tumor xenografts in nude mice [2]. Both McAbs were initially generated against cell surface-assoOffprint requests to: T. Ming Chu ciated components in established human breast tumor cell lines [12].…”