Journal
NATURE MEDICINE
Volume 11, Issue 11, Pages 1230-1237Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm1310
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Funding
- NCI NIH HHS [R21 CA101356-2] Funding Source: Medline
- NHLBI NIH HHS [T32 HL007775] Funding Source: Medline
- NIAID NIH HHS [N01-AI-85342] Funding Source: Medline
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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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