Number of Treatment Cycles Influences Development of Cytotoxic T Cells in Metastatic Breast Cancer Patients – A Phase I/II Study

Abstract

The influence of the number of apheresis-stimulation-infusion(s) cycles, and the time in culture before the infusion (one vs. two weeks), on the generation of tumor antigen-specific cytotoxic T-lymphocytes (CTL) was investigated in a phase I/II clinical adoptive immunotherapy trial. Two previously treated metastatic breast cancer patients 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. Killer T-cells responses against MUC-1-expressing MCF-7 (CTL), nonspecific natural killer (NK) and lymphokine-activated killer (LAK) target cell lines, as well as, cytokine production were measured before each infusion. Patients received 2 infusions per month for 4 months. There were no tumor recurrences or toxicity. CTL, NK and LAK cells, type 1 cytokine, gamma-interferon (G-INF), and CD4⁺ and CD8⁺ memory T-lymphocytes were initially generated, produced or induced, respectively, and then declined. The CTL, NK and LAK cells were only induced at the first infusion of the first month. Thus, maintaining PBMC in culture longer than the first infusion was of no benefit with regards to retaining functional killer T-cells. In conclusion, this study implies that one treatment is optimal.

Keywords:

• Adoptive immunotherapy
• Stimulation
• CTL
• Human
• 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 & 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.