Cancer immunotherapy is considered as the fourth pillar of anti-cancer treatment, along with the traditional three pillars: surgery, radiotherapy, and chemotherapy. Polymers and polymer conjugates have been widely investigated as cancer immunotherapy carriers. The polymeric materials can not only prolong the circulation time of their small molecular cargoes, but also enhance immune activation via multiple mechanisms such as passively or actively targeting immune cells and specific tissue environment. With their great flexibility of monomer selection and post-polymerization modification, polymers and polymer conjugates can satisfy the various needs for immunotherapy. In this dissertation, three different polymer/polymer conjugates have been investigated for facilitating different immunotherapy strategies.pH responsive acetalated dextran microparticles were (Ac-Dex MPs) investigated for the delivery of a high affinity foreign cytotoxic T lymphocyte (CTL) epitope, ovalbumin peptide (OVA), to tumor tissues. Successful OVA delivery to tumor tissue was observed. Both intratumorally and systematically administration of OVA encapsulated Ac-Dex MPs protected mice from pre-established “antigen-loss variant” tumor models. Ultra-pH sensitive nanoparticles (NPs) based on methoxy poly(ethylene glycol)-b-[poly(diisopropylamino)ethyl methacrylate] have been synthesized as a platform for anti-cancer vaccine delivery. Representative CTL antigen OVA and adjuvant imiquimod (IMQ), were covalently conjugated to the polymer backbone through an acid responsive carboxy-dimethylmaleic amide linker (CDM) resulting in polymer P-CDM-OVA and P-CDM-IMQ, respectively. The P-CDM-OVA NPs greatly enhanced CTL responses in vivo compared to the free peptide or the previously reported Ac-Dex MPs encapsulating OVA. Co-administration of P-CDM-OVA NPs with P-CDM-IMQ NPs further improved CTL responses in vivo and effectively reduced tumor growth in mice. Besides serving as delivery carriers, polymers can also be used for surface engineering of immune cells. NK92 cells are a natural killer cell line which is highly cytotoxic, but lack of inherent selectivity toward cancer. We investigated the surface engineering of NK92 with two different strategies: metabolic glycoengineering, and hydrophobic insertion of a polymer grafted with multiple copies of trisaccharide CD22 ligands and a cholesterol terminal. Both methods can successfully modify the surface of NK92 with CD22 ligand and enhance the specific lysis of CD22+ cell lines in vitro. Further investigation of metabolic glycoengineering method showed significant protection against CD22+ tumor in vivo.
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