Cancer-testis antigen SLLP1 represents a promising target for the immunotherapy of multiple myeloma

J Transl Med. 2015 Jun 20:13:197. doi: 10.1186/s12967-015-0562-5.

Abstract

Background: Most patients with multiple myeloma (MM) will relapse after an initial response and eventually succumb to their disease. This is due to the persistence of chemotherapy-resistant tumor cells in the patients' bone marrow (BM) and immunotherapeutic approaches could contribute to eradicating these remaining cells. We evaluated SLLP1 as a potential immunotherapeutic target for MM.

Methods: We determined SLLP1 expression in myeloma cell lines and 394 BM samples from myeloma patients (n = 177) and BM samples from healthy donors (n = 11). 896 blood samples and 64 BM samples from myeloma patients (n = 263) and blood from healthy donors (n = 112) were analyzed for anti-SLLP1 antibodies. Seropositive patients were evaluated regarding SLLP1-specific T cells.

Results: Most cell lines showed SLLP1 RNA and protein expression while it was absent from normal BM. Of 177 patients 41% evidenced SLLP1 expression at least once during the course of their disease and 44% of newly diagnosed patients were SLLP1-positive. Expression of SLLP1 was associated with adverse cytogenetics and with negative prognostic factors including the patient's age, number of BM-infiltrating plasma cells, serum albumin, β2-microglobulin, creatinine, and hemoglobin. Among patients treated with allogeneic stem cell transplantation those with SLLP1 expression showed a trend towards a reduced overall survival. Spontaneous anti-SLLP humoral immunity was detectable in 9.5% of patients but none of the seropositive patients evidenced SLLP1-specific T cells. However, antigen-specific T cells could readily be induced in vitro after stimulation with SLLP1.

Conclusions: SLLP1 represents a promising target for the immunotherapy of MM, in particular for the adoptive transfer of T cell receptor-transduced T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Antibody Formation / immunology
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Cell Line, Tumor
  • Epitopes / immunology
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunoglobulin G / immunology
  • Immunotherapy*
  • Isoantigens / metabolism*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Molecular Targeted Therapy*
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • Phenotype
  • Prognosis
  • Receptors, Antigen, T-Cell / chemistry
  • Seminal Plasma Proteins / metabolism*
  • T-Lymphocytes / immunology
  • Transplantation, Homologous

Substances

  • Epitopes
  • Immunoglobulin G
  • Isoantigens
  • Receptors, Antigen, T-Cell
  • SPACA3 protein, human
  • Seminal Plasma Proteins