Tumor Vaccination with Cytokine-Encapsulated Microspheres

The rapid advances that have taken place in tumor immunology within the past decade have fostered renewed interest in the use of immune-based therapies for the treatment of cancer (1 ,2 ). Numerous strategies, which aim to provoke and augment anti-tumor immunity in cancer patients, have been developed and are being tested in clinical trials (2 –4 ). One strategy that has worked well in preclinical mouse models involves the use of immune stimulatory molecules, i.e., cytokines, to augment the anti-tumor activity of the immune system (5 –7 ). The early studies focused on the systemic administration of selected cytokines to promote a nonspecific augmentation of an already existing anti-tumor immunity (5 ,7 ). While successful in murine models, particularly with interleukin (IL)-2 and -12, the systemic delivery of cytokines has not been efficacious in the clinics due to severe systemic toxicity. Systemic administration of immunotherapeutic agents ignores the paracrine nature of their activity. With the advent of molecular techniques that allowed efficient genetic modification of tumor cells in vitro, cytokine gene-modified tumor cell vaccines became the preferred alternative to systemic therapy. This approach results in the local and sustained release of cytokines by the tumor cells at the vaccine site, which induces the development of a tumor-specific, systemic anti-tumor immunity while circumventing the toxicity associated with systemic delivery (4 –7 ).