Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients

M. Foglietta, S. S. Neelapu, L. W. Kwak, Y. Jiang, D. Nattamai, S. T. Lee, D. H. Fowler, Claude Sportes, R. E. Gress, S. M. Steinberg, L. M. Vence, L. Radvanyi, K. C. Dwyer, M. H. Qazilbash, R. N.K. Bryant, M. R. Bishop

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

To enhance the therapeutic index of allogeneic hematopoietic SCT (HSCT), we immunized 10 HLA-matched sibling donors before stem cell collection with recipient-derived clonal myeloma Ig, idiotype (Id), as a tumor antigen, conjugated with keyhole limpet hemocyanin (KLH). Vaccinations were safe in donors and recipients. Donor-derived KLH- and Id-specific humoral and central and effector memory T-cell responses were detectable by day 30 after HSCT and were boosted by post-transplant vaccinations at 3 months in most recipients. One patient died before booster vaccinations. Specifically, after completing treatment, 8/9 myeloma recipients had persistent Id-specific immune responses and 5/9 had improvement in disease status. Although regulatory T cells increased after vaccination, they did not impact immune responses. At a median potential follow-up period of 74 months, 6 patients are alive, the 10 patients have a median PFS of 28.5 months and median OS has not been reached. Our results provide proof of principle that neoantigen and tumor antigen-specific humoral and cellular immunity could be safely induced in HSCT donors and passively transferred to recipients. This general strategy may be used to reduce relapse of malignancies and augment protection against infections after allogeneic HSCT.

Original languageEnglish (US)
Pages (from-to)269-277
Number of pages9
JournalBone Marrow Transplantation
Volume48
Issue number2
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Fingerprint

Homologous Transplantation
Neoplasm Antigens
Immunity
Vaccination
Tissue Donors
Regulatory T-Lymphocytes
Humoral Immunity
Cellular Immunity
Siblings
Stem Cells
T-Lymphocytes
Transplants
Recurrence
Therapeutics
Infection
Neoplasms
keyhole-limpet hemocyanin

Keywords

  • allogeneic
  • donor vaccination
  • idiotype
  • myeloma

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients. / Foglietta, M.; Neelapu, S. S.; Kwak, L. W.; Jiang, Y.; Nattamai, D.; Lee, S. T.; Fowler, D. H.; Sportes, Claude; Gress, R. E.; Steinberg, S. M.; Vence, L. M.; Radvanyi, L.; Dwyer, K. C.; Qazilbash, M. H.; Bryant, R. N.K.; Bishop, M. R.

In: Bone Marrow Transplantation, Vol. 48, No. 2, 01.02.2013, p. 269-277.

Research output: Contribution to journalArticle

Foglietta, M, Neelapu, SS, Kwak, LW, Jiang, Y, Nattamai, D, Lee, ST, Fowler, DH, Sportes, C, Gress, RE, Steinberg, SM, Vence, LM, Radvanyi, L, Dwyer, KC, Qazilbash, MH, Bryant, RNK & Bishop, MR 2013, 'Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients', Bone Marrow Transplantation, vol. 48, no. 2, pp. 269-277. https://doi.org/10.1038/bmt.2012.132
Foglietta, M. ; Neelapu, S. S. ; Kwak, L. W. ; Jiang, Y. ; Nattamai, D. ; Lee, S. T. ; Fowler, D. H. ; Sportes, Claude ; Gress, R. E. ; Steinberg, S. M. ; Vence, L. M. ; Radvanyi, L. ; Dwyer, K. C. ; Qazilbash, M. H. ; Bryant, R. N.K. ; Bishop, M. R. / Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients. In: Bone Marrow Transplantation. 2013 ; Vol. 48, No. 2. pp. 269-277.
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