| Description |
Cancer vaccines and immune checkpoint antibodies are two types of cancer immunotherapy. This dissertation describes the development of drug delivery systems that can improve the efficacy of vaccines and antibodies for cancer treatment. These drug delivery systems are derived from immune-tolerant elastin-like polypeptide (iTEP), a biocompatible and tunable polymer with a temperature-responsive property. To improve the potency of vaccines, we used iTEP to deliver vaccines to lymph nodes, the major sites where vaccines stimulate immune responses. We also found that iTEP increased the antigen presentation of vaccines in dendritic cells, another mechanism to promote the efficacy of vaccines. Results showed that iTEP enhanced the potency of vaccines by targeting the vaccines to lymph nodes and promoting the antigen presentation. Bypassing the intracellular degradation of vaccines in dendritic cells, a process that has low efficiency and limits the efficacy of vaccines, is another strategy to improve vaccines. Therefore, we designed iTEP to release vaccines at the outside of dendritic cells, reducing vaccines to be degraded at the inside of dendritic cells. The release of vaccines is dependent on an enzyme that is secreted by dendritic cells. Results demonstrated that controlling the release of vaccines promoted the efficacy of a clinically used cancer vaccine. iTEP can also facilitate local delivery of immune checkpoint antibodies. We designed iTEP to form insoluble aggregates at local injection areas at body temperature. The aggregates, similar to drug depots, can trap antibodies at local sites and release the iv antibodies slowly. Animal studies showed that iTEP could concentrate antibodies in tumor tissues for a prolonged time while limiting the diffusion of antibodies to other healthy tissues and the blood. These results suggest that iTEP may increase efficacy and reduce side effects of immune checkpoint antibodies. In summary, iTEP-based drug delivery systems are adjustable to improve various cancer immunotherapeutics, especially cancer vaccines, and immune checkpoint antibodies. |
