title: Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer.
abstract: 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.
authors.affiliation: University of Maryland Greenebaum Cancer Center and Center for Vaccine Development, 22 South Greene Street Baltimore, Maryland 21201, USA. arapoport@umm.edu
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Rapoport
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: Nicole
authors.initials: N
authors.lastname: Aqui
authors.forename: Ashraf
authors.initials: A
authors.lastname: Badros
authors.forename: Julio
authors.initials: J
authors.lastname: Cotte
authors.forename: Lisa
authors.initials: L
authors.lastname: Chrisley
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Veloso
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zheng
authors.forename: Sandra
authors.initials: S
authors.lastname: Westphal
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mair
authors.forename: Nina
authors.initials: N
authors.lastname: Chi
authors.forename: Bashi
authors.initials: B
authors.lastname: Ratterree
authors.forename: Mary Francis
authors.initials: MF
authors.lastname: Pochran
authors.forename: Sabrina
authors.initials: S
authors.lastname: Natt
authors.forename: Joanne
authors.initials: J
authors.lastname: Hinkle
authors.forename: Cheryl
authors.initials: C
authors.lastname: Sickles
authors.forename: Ambika
authors.initials: A
authors.lastname: Sohal
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ruehle
authors.forename: Christian
authors.initials: C
authors.lastname: Lynch
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: David L
authors.initials: DL
authors.lastname: Porter
authors.forename: Selina
authors.initials: S
authors.lastname: Luger
authors.forename: Chuanfa
authors.initials: C
authors.lastname: Guo
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Fang
authors.forename: William
authors.initials: W
authors.lastname: Blackwelder
authors.forename: Kim
authors.initials: K
authors.lastname: Hankey
authors.forename: Dean
authors.initials: D
authors.lastname: Mann
authors.forename: Robert
authors.initials: R
authors.lastname: Edelman
authors.forename: Carl
authors.initials: C
authors.lastname: Frasch
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.forename: Alan
authors.initials: A
authors.lastname: Cross
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008231:Lymphopenia / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D022242:Pneumococcal Vaccines / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D022242:Pneumococcal Vaccines