Immunotherapy for Urologic Tumors

Abstract

Cancer vaccines are intended to promote a long-lasting memory response against tumors.

Rationale for cancer vaccines is based on two observations: a) many tumors express antigens (TA), which are recognized by specific cytotoxic T lymphocytes; b) these lymphocytes may protect the host against tumor growth in vivo.

So far, cancer vaccines have been developed using soluble TA and, more recently, TA presented by dendritic cells (DC), the most powerful antigen presenting cells (APC). DCs play a key role in the process leading to antigen recognition and lymphocyte activation. Despite a deeper understanding of these processes, clinical efficacy of cancer vaccines is still hampered by the heterogeneity of the studies performed so far, and by the largely unknown mechanisms through which tumors escape immunosurveillance.

Current DC-based cancer vaccines require the preparation of DCs from patient blood monocytes, as well as DC-loading with TA. Both whole tumor and TA peptides are used as source of TA. Similar schedules have been implemented in many clinical trials on melanoma, kidney and prostate cancer, with partial responses ranging from 7% to 30%. The study population was made up of non-respondent patients to any other therapy; the DC vaccination showed an extremely low toxicity.

22 patients with metastatic melanoma received a DC vaccine in Forlì (Italy) since August 2001. Good correlation between immunologic response, clinical response and overall survival was found. A clinical trial on pulsed APC administration to patients with recurring prostate cancer is ready to be started in Torino (Italy), pending the Ministerial approval from a local cell factory.