Tumor Burden Influences Cytotoxic T Cell Development in Metastatic Breast Cancer Patients—A Phase I/II Study

Abstract

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.

Keywords:

• Immunotherapy
• Human
• CTL
• Tumor burden
• MUC1

ACKNOWLEDGMENTS

The authors are grateful to those mentioned in the text for supplying materials, Brian Pruitt for referring patients and support, Coffee Memorial Blood Bank, Amarillo, TX, for apheresis, Robin McWherter and Beth Vertin for technical assistance, the Clinical Trials Department of the Harrington Cancer Center, Amarillo, TX, for data collection, and to Jeremiah Bresnahan and Ray Sisneros, for clerical assistance, Zhenyao Wang for computer graphics assistance, and Candace Myers for editorial assistance. This work was supported in part by The Don and Sybil Harrington Foundation, Amarillo, TX, and Department of Veterans Affairs Medical Research funds (SEW).

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.