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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 48; no. 2; pp. 269 - 277
• Main Authors: Foglietta, M, Neelapu, S S, Kwak, L W, Jiang, Y, Nattamai, D, Lee, S-T, Fowler, D H, Sportes, C, Gress, R E, Steinberg, S M, Vence, L M, Radvanyi, L, Dwyer, K C, Qazilbash, M H, Bryant, R N K, Bishop, M R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2013; Nature Publishing Group
• Subjects: 631/250/1904; 631/532/1542; 692/699/67/1990/804; 692/700/565/251/1567; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - immunology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone marrow; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Cancer; Care and treatment; Cell Biology; Cell-mediated immunity; Donors; Dosage and administration; Epitopes; Female; Health aspects; Hematologic and hematopoietic diseases; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Hemocyanins; Hemocyanins - administration & dosage; Hemocyanins - immunology; Hemopoiesis; Histocompatibility antigen HLA; Histocompatibility antigens; HLA Antigens - immunology; HLA histocompatibility antigens; Humans; Humoral immunity; Idiotypes; Immunity; Immunity (cell-mediated); Immunity, Cellular - immunology; Immunization; Immunization - methods; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin Idiotypes - administration & dosage; Immunoglobulin Idiotypes - immunology; Immunoglobulinopathies; Immunoglobulins; Immunological memory; Immunopathology; Immunoregulation; Infection; Internal Medicine; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes T; Male; Malignancy; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - immunology; Multiple Myeloma - surgery; Multiple Myeloma - therapy; Myeloma; Neoantigens; original-article; Patients; Physiological aspects; Public Health; Siblings; Stem cell transplantation; Stem Cells; Tissue Donors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Immunology; Transplantation, Homologous; Transplants & implants; Tumors; Vaccination; Vaccines; United States; donor vaccination; idiotype; myeloma; allogeneic; Human; Immunopathology; Tumor specific antigen; Hematology; Stem cell; Vaccination; Hematopoietic cell; Homograft; B cell neoplasm; Malignant hemopathy; Lymphoid neoplasm; Myeloma; Immunity; Prevention; Immunoglobulinopathy; Donor; Lymphoproliferative syndrome; Graft; Early; Neoantigen; Cancer; Idiotype
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2012.132

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.