The direct display of costimulatory proteins on tumor cells as a means of vaccination for cancer immunotherapy

Abstract

Therapeutic vaccines against cancer are at their prime, owing to our comprehensive understanding of immune effector responses generated against tumor and the mechanisms employed by the progressing tumor to evade the immune system. The immune system is primed by tumor-associated antigens (TAA) that are perceived as foreign. Therefore, the identification of TAA led to the development of subunit vaccine formulations comprising defined TAA as stand-alone vaccines or in combination with immune adjuvants. Inasmuch as cancer cells express a diverse set of TAA, novel immunomodulatory approaches that not only use tumor cells as a source of diverse TAA but also convert them into competent antigen-presenting cells have significant therapeutic potential as cell-based vaccines. Toward this end, we have developed a novel protein display approach designated as ProtEx™ as a safe and efficient alternative to DNA-based gene expression to generate novel immunomodulatory molecules and display them on tumor cells for the development of cancer vaccines. This chapter describes the ProtEx™ technology and its application to the generation of tumor cell-based cancer vaccines.