Tetanus Toxoid and CCL3 Improve DC Vaccines

摘要

Pre-conditioning a vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DC vaccines. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokines CCL3 and CCL21 and Td-activated CD4+ T cells. Interference with any component of this axis markedly reduced Td-mediated DC migration and antitumor responses. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen represents a viable strategy to increase DC homing to lymph nodes and improve antitumor immunotherapy.

主权项

1. A method of immunizing a human, comprising:
administering a first acellular immunogen to the human; and administering a second immunogen to the human,whereby administration of the first immunogen increases migration of the second immunogen to vaccine draining lymph nodes (VLDNs), wherein the first acellular immunogen is not an inflammatory cytokine, wherein the first and second immunogens are distinct, wherein the human has been previously immunized with or exposed to the first immunogen and wherein the human has memory T cells which are specific and responsive to the first immunogen.