Coencapsulation of tumor lysate and CpG-ODN in PLGA-microspheres enables successful immunotherapy of prostate carcinoma in TRAMP mice

Abstract

Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres (MS) deliver antigens and toll like receptor (TLR) ligands to antigen presenting cells (APC) in vitro and in vivo. PLGA-MS-microencapsulated model antigens are efficiently presented on MHC class I and II molecules of dendritic cells and stimulate strong cytotoxic and T helper cell responses enabling the eradication of pre-existing model tumors. The application of tumor lysates as a source of antigen for immunotherapy has so far not been very successful also due to a lack of suitable delivery systems. In this study we used PLGA-MS with co-encapsulated tumor lysates and CpG oligodeoxynucleotides (CpG-ODN) as well as microencapsulated polyI:C in order to elicit anti-tumor responses. Immunization of mice with such mixtures of MS yielded substantial cytotoxic T cell (CTL) responses and interfered with tumor growth in TRAMP mice, a pre-clinical transgenic mouse model of prostate carcinoma, which has previously resisted dendritic cell-based therapy. As an important step towards clinical application of PLGA-MS, we could show that γ-irradiation of PLGA-MS sterilized the MS, without reducing their efficacy in eliciting CTL and anti-tumor responses in subcutaneous tumor grafts. Since PLGA is approved for clinical application, sterilized PLGA-MS containing tumor lysates and TLR ligands hold promise as anti-tumor vaccines against prostate carcinoma in humans.

Personalized approaches to active immunotherapy in cancer

“…has recently demonstrated the potential of tumor lysate and TLR ligand coencapsulation in a highly tolerized prostate cancer murine model [120]. In this study, PLGA particles, co-encapsulating CpG and tumor lysate, were administrated to mice and induced potent long lasting CTL responses and significant tumor growth arrest [120].…”

Cutting Edge: A Dual TLR2 and TLR7 Ligand Induces Highly Potent Humoral and Cell-Mediated Immune Responses

“…1C). These findings suggest that PamadiFectin may be especially useful as an adjuvant in the setting of therapeutic vaccination, where the induction of cytotoxic responses is paramount in the fight against cancer and chronic infections (23).…”

Biodegradable Polymeric Nanoparticles-Based Vaccine Adjuvants for Lymph Nodes Targeting

“…The use of PLGA microspheres (1–10 µm) carrying tumor lysates and TLR9 ligand CpG ODN is promising as an anti-tumor vaccine against prostate carcinoma. Indeed, the co-encapsulation of tumor lysates with CpG-ODN induces high cytotoxic responses, leading to a reduction in tumor growth in a mouse model of prostate carcinoma [61]. Biodegradable polymeric NPs are a good alternative to adjuvants based on mineral oils that can be accompanied with adverse effects.…”