title: Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients.
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.
authors: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: M
authors: M
authors: Foglietta
authors: S S
authors: SS
authors: Neelapu
authors: L W
authors: LW
authors: Kwak
authors: Y
authors: Y
authors: Jiang
authors: D
authors: D
authors: Nattamai
authors: S-T
authors: ST
authors: Lee
authors: D H
authors: DH
authors: Fowler
authors: C
authors: C
authors: Sportes
authors: R E
authors: RE
authors: Gress
authors: S M
authors: SM
authors: Steinberg
authors: L M
authors: LM
authors: Vence
authors: L
authors: L
authors: Radvanyi
authors: K C
authors: KC
authors: Dwyer
authors: M H
authors: MH
authors: Qazilbash
authors: R N K
authors: RN
authors: Bryant
authors: M R
authors: MR
authors: Bishop
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000939:Epitopes; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology* / Q000601:surgery / Q000628:therapy*; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D006680:HLA Antigens; D007130:Immunoglobulin Idiotypes; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin