Anti-cancer immune-therapy is recognized as one of the most promising strategies for treatment of metastatic cancer. It practices the patient’s own defense mechanism by activating it in such a way that it recognizes and eliminates malignant cells. Here we report an innovative generic strategy for the encapsulation of patient-specific cancer antigens into particles. This approach covers a broad range of tumor-associated antigens and enables the induction of specific routes of cell-death potentially leading to more specific, more efficient and more potent immune activation of the patient. First, we demonstrate in situ encapsulation of live whole cancer cells into polymeric microcapsules followed by killing of the cancer cells and release of the cancer cell lysate into the hollow void of the capsules. Live B16 melanoma cells were used as a cancer model and were coated in a Layer-by-Layer (LbL) fashion with alternating layers of poly(vinylpyrrolidone) (PVP) and tannic acid (TA) using hydrogen bonding as driving force for multilayer assembly. Fine-tuning of the assembly conditions was assessed by real-time flow cytometry, fluorescence microscopy, SDS-PAGE and TEM and allowed us to obtain cell-templated bio-hybrid capsules containing a high amount of encapsulated proteins. Second, contrary to the in situ encapsulation of cancer cells, we explore the conjugation of cell lysate to polymers. A copolymer composed of hydroxypropyl methacrylamide and aminopropyl methacrylamide (HPMA-co-APMA) via RAFT polymerization was synthesized. Disulfide or maleimide groups were introduced to allow interaction with cancer cell lysate respectively via reversible thiol-disulfide exchange or Michael addition. High encapsulation efficiencies were visualized and the (ir)reversible binding properties were confirmed by SDS-PAGE.

Polymeric strategies for the encapsulation of cell lysates in view of anticancer immunotherapy

249th National Meeting (2015)

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