Immunomodulation of Hyperthermia for Recurrent Prostate Cancer

摘要

There is currently no curative treatment for recurrent hormonally refractive prostate cancer (PC). Radiation therapy (RT) has been used successfully in the treatment of primary PC, however it is not used to treat locally recurrent PC because of the high morbidity of additional pelvic irradiation and the radiation sensitivities of adjacent normal tissues. Hyperthermia has undergone extensive study as a treatment for BPH and its safety is very well established. Our goal is to develop a treatment strategy utilizing hyperthermia as an adjunct tumoricidal therapy for recurrent PC. We propose an in situ tumor vaccination approach where irradiated/heated tumor cells release peptides/antigens following localized treatment while in vivo cytokine-stimulated dendritic cells (DCs) or intratumoral injection of in vitro derived autologous DCs (bone marrow generated) harvest these antigens resulting in an effective tumor-specific immunity. This proposal has the following specific aims: (1) To determine whether DCs are activated following antigen uptake from PC cells treated with hyperthermia; (2) To determine whether DC-stimulating cytokines (GM-CSF, Flt3L and CD40L) following local hyperthermia of primary tumor induce specific immunity and improve local and distant tumor regression; (3) To determine DC activation after antigen uptake is dependent upon preexisting microenvironment of PC.