These compounds can be used in the treatment of neoplastic disease. They are useful as adjuvant compositions to increase cell-mediated immunity for the treatment of tumors and as an adjuvant for vaccines.
The immune system mounts a strong response when foreign objects are detected within the body. This is not only the premise for fighting foreign invaders, but is the underlying basis for vaccines, as they must induce an immune response in order for the body to produce antibodies to the desired antigen. Some antigens are highly immunogenic and are capable of eliciting a protective immune response. In other cases, the antigens fail to induce a protective immune response or induce only a weak response. Immunopotentiators, or adjuvants, of vaccines have been used for some time to facilitate a stronger immune response to a vaccine. There are several different methods used to achieve this stronger immune response including mobilizing T cells, acting as depots and altering lymphocyte circulation and allowing antigen specific T cells and B cells to interact more efficiently with antigen-presenting cells.
Many tumors express proteins that can serve as tumor-specific antigens. However, tumors generally lack co-stimulatory molecules and therefore cannot provide the requisite two signals to activate the appropriate immune cascade. Consequently, spontaneous tumors generally fail to stimulate an immune response. Dr. Kapp's group has recently found that the antitussive noscapine and its derivatives are useful in the treatment of neoplastic disease. By arresting mammalian cells at mitosis, noscapine causes apoptosis in cycling cells and has potent antitumor activity. Noscapine has also been shown to promote assembly of tubulin subunits. In addition to its direct anti-proliferative activity on tumors, noscapine has also been shown to augment immune responses to the tumor. The dual action of noscapine promises to be an improvement to current therapeutic agents that only a kill the tumor because such agents rarely if ever remove all residual tumor cells. Tumor-specific immune responses should provide the means to remove residual tumor cells and prevent recurrence of latent tumors.
An alkaloid derived from opium, noscapine is readily available as a commercial byproduct in the production of prescription opiates and has a low toxicity in humans.