The goals of the present study were to: (1) define the effects of simultaneous cisplatin/ tecemotide therapy on tumor development in a human mucin 1 (MUC1) transgenic lung cancer mouse model; and (2) examine the effects of radiation therapy (RTX) on splenocytes, serum cytokines, and immune response to tecemotide. Two hundred twenty-six human MUC1 transgenic mice were used in five studies designed to assess: (1) serum cytokine and immune responses following four weekly 10-µg doses of tecemotide; (2) effects of simultaneous administration of cisplatin (2.5 mg/kg x 2 doses/cycle x 4 cycles) and tecemotide (2 cycles x 8 weekly 10-µg doses/cycle) therapy on tumor development, serum cytokines and immune response; (3) dose response effects of RTX on lymphocyte counts 16 h following doses of 2-8 Gy; (4) time course of lymphocyte recovery from 16 h to 20 d following 8 Gy RTX; and (5) effects of simultaneous administration of RTX (8 Gy) and tecemotide on immune response to tecemotide (4 weekly 10-µg doses). Serum cytokines were analyzed by multiplex immunoassay, interferon gamma (IFN-γ) immune responses by ELISpot, and lung tumor foci by lung whole mounts. Simultaneous cisplatin/tecemotide therapy resulted in significant and additive reduction in lung tumor foci compared to control mice, with significantly elevated serum IFN-γ levels and specific IFN-γ immune responses observed in both tecemotide and tecemotide + cisplatin treated mice. Finally, neither cisplatin nor radiation interfered with the immune response to tecemotide.
- Received November 19, 2013.
- Revision received February 14, 2014.
- Accepted February 27, 2014.
- Copyright © 2014, American Association for Cancer Research.