Influence of estradiol and tamoxifen on susceptibility of human breast cancer cell lines to lysis by lymphokine-activated killer cells.
The design of combination hormonal and immunotherapeutic protocols for breast cancer patients may be facilitated by analysis of preclinical in vitro model systems. Estrogen receptor positive (ER+: MCF-7) and negative (ER-: MDA-MB-231) human breast cancer cell lines were utilized to evaluate the effects of tamoxifen (TAM) and estradiol (E2) on modulation of breast cancer target susceptibility to lysis by lymphokine-activated killer (LAK) cells. E2-stimulated ER+ cells were more susceptible to lysis by LAK cells than corresponding TAM-treated or control cells, while treatment of ER- cells with either E2 or TAM alone did not alter from control their susceptibility to this immune-mediated lysis. All ER+ and ER- cells tested remained sensitive after treatment with TAM to lysis by LAK cells. In addition, an adenocarcinoma reactive human-mouse chimeric monoclonal antibody (ING-1) was able to significantly boost in vivo generated LAK cell-mediated lysis of control, E2-treated, and TAM-treated ER+ and ER- cells. These in vitro results provide a preclinical rationale for in vivo testing of TAM, interleukin-2 (IL-2), and breast cancer reactive antibody-dependent cellular cytotoxicity facilitating antibody in patients with refractory or high risk breast cancer.
Albertini
M R
MR
Department of Human Oncology, University of Wisconsin, Madison 53792.
Gibson
D F
DF
Robinson
S P
SP
Howard
S P
SP
Tans
K J
KJ
Lindstrom
M J
MJ
Robinson
R R
RR
Tormey
D C
DC
Jordan
V C
VC
Sondel
P M
PM
D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D002453:Cell Cycle; D003131:Combined Modality Therapy; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008954:Models, Biological; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol