western blotting showed only Erk1/2 and Akt activation to be

The mix of vaccine and one dose of Y 90 described anti CEA mAb triggered a statistically significant escalation in survival of tumor bearing rats over either method alone. Additionally, the combination group exhibited a substantial Lapatinib increase in the proportion of viable tumor infiltrating CEAspecific CD8 T cells compared to the vaccine alone group. Remarkably, the tumorinfiltrating T-cells were unaffected by the residential light being emitted by the radiolabeled mAb. This finding was in keeping with a preclinical review by Grayson et al. which discovered that murine memory T cells are far more resistant to apoptosis than naive T cells after entire body irradiation. As seen with EBRT, mice healed of tumors also demonstrated an antigen cascade. 32 Brachytherapy Brachytherapy involves implanting a radiation source into or near the site of a malignant tumor to target tumor cells with continuous high-dose radiation. A single study reported the power of iodine 125 and a recombinant poxviral vaccine to modulate tumor cell phenotype and boost antigen specific killing of Organism tumor cells. 33 While more comprehensive studies are essential to validate these results, they do suggest a clinical role for that mixture of brachytherapy and cancer vaccines. In conclusion, a growing human anatomy of evidence suggests that a suitable dose of radiation may have immunomodulatory effects capable of activating the immune system and consequently enhancing immune mediated attack on tumor cells. Several preclinical studies have demonstrated that cancer and radiotherapy vaccines combined work synergistically to generate more robust antitumor effects. 1, 13, 17, 18, 31, 34 Promising from these pre-clinical studies have led to several clinical studies. As the field of cancer therapy advances, monotherapies may fall into disfavor. Actually, many preclinical and clinical studies have combined more than 2 therapeutic modalities. One murine study combined vaccine, local radiation, and reduction of immune suppressor cells,35 while an Apremilast in vitro study reported the combination of systemic multiagent chemotherapy with 5 fluorouracil and cisplatin with tumor irradiation for the treatment of head/neck squamous cell carcinoma. 36 COMBINING CHEMOTHERAPY AND IMMUNOTHERAPY The clinical efficacy of standard of care chemotherapy routines relies mainly on direct cytotoxicity to cancer cells. Until recently, it had been generally believed that after used in combination with a cancer vaccine, chemotherapy would invariably have a negative impact on vaccine mediated antitumor activity and immune responses. 37 Nevertheless, mounting evidence suggests that certain chemotherapeutic agents have immunomodulatory properties that might be used to enhance vaccine mediated anti-tumor effects. This synergy could be mediated by multiple mechanisms, depending on the type of the particular vaccine employed and cytotoxic agent, as well as the dosing schedule of each modality.