32 research outputs found
Activation of cellular immunity after intracavitary monoclonal antibody therapy of ovarian cancer
Background. Murine monoclonal antibodies (MoAbs) are now used for targeted tumor therapy. A major obstacle in their successful application is the development of a humoral antiglobulin response, which limits the use of repeated cycles of therapy. The cellular aspects of that response are not well understood. Methods. Fifteen patients who had one (12 patients) or two (3 patients) courses of MoAb treatment, 13 agematched patients with the same histologic types of tumors who had not received MoAbs, and 4 healthy control subjects were studied. Peripheral blood mononuclear cells (PBMCs) were obtained and tested for the ability of Tâcells to proliferate in vitro in the presence of the MoAb administered for therapy (HMFG1), a control antibody (11.4.1), and, in some cases, their F(ab)2 fragments. In addition, PBMCs from these patients were phenotyped after in vitro MoAb stimulation with antibodies against CD2, CD3, CD4, CD8, CD16, CD20, CD25 (interleukinâ2 receptor [ILâ2R]), CD45RA, and UCHL1, and the production of interleukinâ2 (ILâ2) was evaluated by the CTLLâ2 bioassay. Results. A doseâdependent in vitro Tâcell proliferation was observed in 13 of the 15 patients after MoAb therapy. This was not observed in the pretherapy group of patients or healthy control subjects. The mean stimulation index (SI) in the posttherapy group was significantly higher than that of the pretherapy patients and that of healthy control subjects (P = 0.007). When the in vitro Tâcell proliferative responses of these patients were measured in the presence of HMFG1 MoAb (IgG1) and 11.4.1 MoAb, there was no significant difference in the mean SI for HMFG1 versus 11.4.1 for the whole group of treated patients (P = 0.67). A significant increase in the mean SI was observed in the presence of HMFG1 over 11.4.1 and their F(ab)2 fragments (P = 0.02) in patients treated twice. A significant increase in the percentage of cells expressing ILâ2R was observed after in vitro MoAb stimulation. CD4+ lymphocytes, particularly the CD4+/UCHL1+ memory, the CD4+/ILâ2R+ subpopulation, and the CD4/CD8 ratio, increased in all the cases studied after MoAb stimulation, where Bâcell and natural killerâcell numbers remained relatively constant (<2â3%). A sixfold increase was found in the production of ILâ2 in PBMC supernatants after MoAb stimulation. Conclusions. Mouse MoAbs administered to patients with cancer can lead to the generation of Tâcells, which can recognize these MoAbs as antigens and therefore refocus the host's cellular immune response against the targeted tumor. The main proliferating population appears to be CD4+ Tâlymphocytes, which after stimulation can release ILâ2. Multiple treatments may lead to the generation of Tâcells with specificity for the idiotypic component of the administered MoAb. Cancer 1994; 73:3000â10. Copyright © 1994 American Cancer Societ