Combining AIET with chemotherapy - lessons learnt from our experience

Abstract

Breast cancer is the most common invasive cancer in women and as per the data in 2008, this deadly cancer was responsible for 458,503 deaths worldwide in 2008 [1]. Several researches are on-going for identifying therapeutic strategies for breast cancer. Breast cancer biology is complex and breast cancer stem cells that are often resistant to conventional therapies like chemotherapy [2] increases the complexity as it has been reported that at even early stages of the disease, a portion of the breast cancer cells may have eloped to the bone marrow facilitated by the mesenchymal stem cells [3] and remain dormant becoming active later thereby causing recurrence or advancement of the disease. Natural Killer (NK) cell based Autologous Immune Enhancement Therapy (AIET) which has been administered for different types of cancers [4,5] represents a potential option, as NK cells being a part of innate immunity help in tackling circulating cancer cells [6] and cancer stem cells [7] thereby helping to prevent metastasis. Herein we report our experience of NK cell based AIET in a patient of stage III A breast cancer (inflammatory type) diagnosed three months post-partum. A 29 year old female with history of pain and tenderness in the left breast post-partum was investigated in October 2012 and the investigations revealed the presence of infiltrating ductal carcinoma (pT3 N2a Mx- Stage III A) (T4bN2M0) and the cancer was ER positive, PR negative, Her2neu negative, Ki67 positive (86% of the tumour cells) and EGFR, Cytokeratin 5 negative. The patient underwent three cycles of pre-operative chemotherapy (from October 2012 to December 2012) using Doxorubicin, Docetaxel and Cyclophosphamide followed by left modified radical mastectomy (December 2012) and then three cycles of post-operative chemotherapy (from January to February 2013). The patient simultaneously underwent 12 transfusions of NK cell based AIET from November 2012 to February 2013 planned in accordance with the chemotherapy cycles. Approximately 200-220 ml of peripheral blood (PB) was withdrawn for the first three cycles (three transfusions in one cycle – nine transfusions in total) and then for the 10th transfusion, only 40 ml of PB was withdrawn as the patient's general health condition was low. 185 ml of PB was withdrawn for the 11th and 12th transfusions. For each AIET transfusion, the NK cells isolated from peripheral blood monononuclear cells (PBMNCSs) were culture-expanded in vitro based on earlier described protocols [8, 9] for 10-12 days before being infused to the patient. Chemotherapy has earlier been reported to cause a decline in NK cell number and function [10]. It was observed in the present case that, with progressively increasing number of chemotherapy cycles, there was a gradual decline in the in vitro growth expansion of the NK cells, though the number of NK cells isolated from the peripheral blood remained fairly constant. After AIET and chemotherapy, the patient underwent radiotherapy with 5400cGy in 27 fractions. The patient is under follow-up. The decrease in NK cell expansion potential with progressive chemotherapy implies a weakened immune system after chemotherapy. This experience could be an eye opener to understand the potential weakness of the immune system with the present therapies enable us undertake researches to come out with more targeted therapies which shall not compromise the immune system thereby plugging the loopholes to prevent metastases and to yield a better prognosis.