Nature Medicine 11, 1230 - 1237 (2005)
Published online: 16 October 2005; | doi:10.1038/nm1310
Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transferAaron P Rapoport1, 4, Edward A Stadtmauer2, 4, Nicole Aqui2, 4, Ashraf Badros1, Julio Cotte2, Lisa Chrisley1, Elizabeth Veloso2, Zhaohui Zheng2, Sandra Westphal1, Rebecca Mair2, Nina Chi2, Bashi Ratterree1, Mary Francis Pochran1, Sabrina Natt1, Joanne Hinkle2, Cheryl Sickles2, Ambika Sohal2, Kathleen Ruehle1, Christian Lynch3, Lei Zhang1, David L Porter2, Selina Luger2, Chuanfa Guo1, Hong-Bin Fang1, William Blackwelder1, Kim Hankey1, Dean Mann1, Robert Edelman1, Carl Frasch3, Bruce L Levine2, 4, Alan Cross1, 4
& Carl H June2, 41
University of Maryland Greenebaum Cancer Center and Center for Vaccine Development, 22 South Greene Street Baltimore, Maryland 21201, USA. 2
Abramson Cancer Center, University of Pennsylvania, 421 Curie Boulevard Philadelphia, Pennsylvania 19104, USA. 3
Food and Drug Administration, Center for Biologics Evolution and Research, 1401 Rockville Pike, Rockville, Maryland 20852, USA. 4
These authors contributed equally to this work.
Correspondence should be addressed to Aaron P Rapoport arapoport@umm.edu or Carl H June cjune@mail.med.upenn.edu Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a single early post-transplant infusion of in vivo vaccine-primed and ex vivo costimulated autologous T cells followed by post-transplant booster immunizations improved the severe immunodeficiency associated with high-dose chemotherapy and led to the induction of clinically relevant immunity in adults within a month after transplantation. Immune assays showed accelerated restoration of CD4 T-cell numbers and function. Early T-cell infusions also resulted in significantly improved T-cell proliferation in response to antigens that were not contained in the vaccine, as assessed by responses to staphylococcal enterotoxin B and cytomegalovirus antigens (P < 0.05). In the setting of lymphopenia, combined vaccine therapy and adoptive T-cell transfer fosters the development of enhanced memory T-cell responses.
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