The goals of the present study were to define the effects of simultaneous cisplatin/tecemotide therapy on tumor development in a human mucin 1 (MUC1) transgenic lung cancer mouse model and to examine the effects of radiotherapy (RTX) on splenocytes, serum cytokines, and immune response to tecemotide. Two hundred twenty-six human MUC1 transgenic C57BL/6 mice were used in five studies designed to assess (i) serum cytokine and immune responses following four weekly 10-μg doses of tecemotide; (ii) the effects of simultaneous administration of cisplatin (2.5 mg/kg × 2 doses/cycle × 4 cycles) and tecemotide (2 cycles × 8 weekly 10-μg doses/cycle) therapy on tumor development, serum cytokines, and immune response; (iii) the dose-response effects of RTX on lymphocyte counts 16 hours following doses of 2 to 8 Gy; (iv) the time course of lymphocyte recovery from 16 hours to 20 days following 8-Gy RTX; and (v) the effects of simultaneous administration of RTX (8 Gy) and tecemotide on the immune response to tecemotide (four weekly 10-μg doses). Serum cytokines were analyzed by multiplex immunoassay, IFNγ immune responses by enzyme-linked immunosorbent spot (ELISpot), and lung tumor foci by lung whole mounts. Simultaneous cisplatin/tecemotide therapy resulted in significant and additive reduction in lung tumor foci compared with control mice, with significantly elevated serum IFNγ levels and specific IFNγ immune responses observed in both tecemotide and tecemotide + cisplatin-treated mice. Finally, neither cisplatin nor radiation interfered with the immune response to tecemotide.