Tumor burden influences cytotoxic T cell development in metastatic breast cancer patients--a phase I/II study.
The influence of tumor burden on the generation of tumor antigen-specific cytotoxic T-lymphocytes (CTL) was investigated in a phase I/II clinical adoptive immunotherapy trial. Four previously treated metastatic breast cancer patients, two with macroscopic disease and two with no evidence of disease, in complete remission (CR), were enrolled. Each apheretic peripheral blood mononuclear cell (PBMC) sample was stimulated twice with MUC-1 before infusion back into the patients. CTL responses against MCF-7 cell line and cytokine production were measured before infusion. Patients received two monthly CTL infusions and were monitored for toxicity, tumor response as well as tumor marker levels. The CTL generated from patients with high tumor burdens had less cytokine production and lower cytotoxicity of MCF-7 than the CTL of patients in CR. The differences between the two groups were observed after the two MUC1 in vitro stimulations of the cells obtained in first apheresis. This difference increased after the two MUC1 stimulations of the cells obtained in the second apheresis. The cytotoxicity function was sustained from the first infusion to the second apheresis only for the patients in CR. This suggests that tumor burden had an inverse effect on the function of the generated CTL.
Medical Service, Amarillo Veterans Affairs Health Care System, Amarillo, TX 79106, USA. stephen.wright@med.va.gov
Stephen E
SE
Wright
Kathleen A
KA
Rewers-Felkins
Imelda S
IS
Quinlin
Catherine A
CA
Phillips
Mary
M
Townsend
Ramila
R
Philip
Paul
P
Zorsky
Panpit
P
Klug
Lijun
L
Dai
Mohammad
M
Hussain
Aabu A
AA
Thomas
Chithraleka
C
Sundaramurthy
D014408:Biomarkers, Tumor / Q000378:metabolism; D001804:Blood Transfusion, Autologous; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D017708:Leukocyte Transfusion; D007963:Leukocytes, Mononuclear; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology*; D009362:Neoplasm Metastasis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden / Q000276:immunology*
D014408:Biomarkers, Tumor; D016207:Cytokines; C060192:MUC1 protein, human; D018396:Mucin-1