Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer.
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.
Rapoport
Aaron P
AP
University of Maryland Greenebaum Cancer Center and Center for Vaccine Development, 22 South Greene Street Baltimore, Maryland 21201, USA. arapoport@umm.edu
Stadtmauer
Edward A
EA
Aqui
Nicole
N
Badros
Ashraf
A
Cotte
Julio
J
Chrisley
Lisa
L
Veloso
Elizabeth
E
Zheng
Zhaohui
Z
Westphal
Sandra
S
Mair
Rebecca
R
Chi
Nina
N
Ratterree
Bashi
B
Pochran
Mary Francis
MF
Natt
Sabrina
S
Hinkle
Joanne
J
Sickles
Cheryl
C
Sohal
Ambika
A
Ruehle
Kathleen
K
Lynch
Christian
C
Zhang
Lei
L
Porter
David L
DL
Luger
Selina
S
Guo
Chuanfa
C
Fang
Hong-Bin
HB
Blackwelder
William
W
Hankey
Kim
K
Mann
Dean
D
Edelman
Robert
R
Frasch
Carl
C
Levine
Bruce L
BL
Cross
Alan
A
June
Carl H
CH
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
D022242:Pneumococcal Vaccines