Improving methods for immunomodulation in cancer therapy
Immunostimulatory cytokines such as tumor necrosis factor and interferon-alpha have been documented to exert powerful anti-cancer effects. Unfortunately, these cytokines’ capacity to evoke potent and pleiotropic responses has hampered their use in the clinic; systemic administration often leads to severe side effects, which limit dosage amounts. Antibody-cytokine fusions have been constructed to increase treatment specificity, yet these immunoconjugates also have disadvantages, including immunogenicity and systemic toxicity due to long serum half-lives. We are exploring strategies to minimize the problems of dose-limiting toxicity and low therapeutic indices in current cytokine therapies.