Engineered red blood cells (activating antigen carriers) drive potent T cell responses and tumor regression in mice.

Activation of T cell responses is essential for effective tumor clearance; however, inducing targeted, potent antigen presentation to stimulate T cell responses remains challenging. We generated Activating Antigen Carriers (AACs) by engineering red blood cells (RBCs) to encapsulate relevant tumor antigens and the adjuvant polyinosinic-polycytidylic acid (poly I:C), for use as a tumor-specific cancer vaccine. The processing method and conditions used to create the AACs promote phosphatidylserine exposure on RBCs and thus harness the natural process of aged RBC clearance to enable targeting of the AACs to endogenous professional antigen presenting cells (APCs) without the use of chemicals or viral vectors. AAC uptake, antigen processing, and presentation by APCs drive antigen-specific activation of T cells, both in mouse in vivo and human in vitro systems, promoting polyfunctionality of CD8+ T cells and, in a tumor model, driving high levels of antigen-specific CD8+ T cell infiltration and tumor killing. The efficacy of AAC therapy was further enhanced by combination with the chemotherapeutic agent Cisplatin. In summary, these findings support AACs as a potential vector-free immunotherapy strategy to enable potent antigen presentation and T cell stimulation by endogenous APCs with broad therapeutic potential.

Vaccine prospects for amebiasis.

Entamoeba histolytica is a eukaryotic protozoan parasite and is the causative agent of amebic colitis and amebic liver abscess. Many insights into the innate and acquired immune responses to infection with E. histolytica have been made in recent years. These findings have provided a foundation for producing a vaccine that could help to prevent the initial establishment of infection in the intestinal wall. The galactose and N-acetyl-D-galactosamine-specific lectin on the surface of the ameba is an immunodominant molecule that is highly conserved and has an integral role in the stimulation of these immune responses. The structure of the lectin has been defined, and the heavy subunit with its cysteine-rich region has been demonstrated in animal models to have some efficacy as a possible vaccine agent for prevention of amebic infection. Finding an ideal animal model of amebic intestinal infection has been difficult, but the C3H mouse and severe combined immunodeficient mouse-human intestinal xenograft models have both provided valuable insights into the first line of immune defense at the mucosal wall of the colon. Providing safe food and water to all people in the developing world is a formidable task that is not achievable in the foreseeable future. However, a vaccine for amebiasis could make a significant impact on the morbidity and mortality from the disease. Many components of the ameba are immunogenic and may serve as targets for a future vaccine, including the galactose and N-acetyl-D-galactosamine lectin, the serine-rich E. histolytica protein, cysteine proteinases, lipophosphoglycans, amebapores and the 29-kDa protein.