Myeloma cell line–derived, pooled heat shock proteins as a universal vaccine for immunotherapy of multiple myeloma
- 29 October 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 114 (18), 3880-3889
- https://doi.org/10.1182/blood-2009-06-227355
Abstract
Tumor cell–derived heat shock proteins are used as vaccines for immunotherapy of cancer patients. However, current approaches require the generation of custom-made products and are clinically ineffective. To improve the applicability of heat shock protein–based immunotherapy in cancers and to enhance clinical efficacy, we explored combinational treatments in a myeloma setting using pooled heterogeneous or allogeneic myeloma cell line–derived glycoprotein 96 (gp96) as universal vaccines, and clearly demonstrated that pooled but not single gp96 from heterogeneous or allogeneic myeloma cell lines was as effective as autologous gp96 in protecting mice from tumor challenge and rechallenge and in treating established myeloma. We showed that interferon γ and CD4+ and CD8+ T cells were required for gp96-induced antimyeloma responses and that pooled gp96 induced broader immune responses that protected mice from developing different myeloma. Furthermore, pooled gp96 plus CpG in combination with anti-B7H1 or anti–interleukin-10 monoclonal antibodies were effective in treating mice with large tumor burdens. Thus, this study strongly suggests that pooled gp96 vaccines from myeloma cell lines can replace gp96 vaccines from autologous tumors for immunotherapy and induce immune responses against broader tumor antigens that may protect against tumor recurrence and development of unrelated tumors in vaccinated myeloma patients.Keywords
This publication has 60 references indexed in Scilit:
- Functional islet‐specific Treg can be generated from CD4+CD25− T cells of healthy and type 1 diabetic subjectsEuropean Journal of Immunology, 2009
- Phase III Comparison of Vitespen, an Autologous Tumor-Derived Heat Shock Protein gp96 Peptide Complex Vaccine, With Physician's Choice of Treatment for Stage IV Melanoma: The C-100-21 Study GroupJournal of Clinical Oncology, 2008
- CpG oligodeoxynucleotides induce cyclooxygenase-2 in human B lymphocytes: Implications for adjuvant activity and antibody productionClinical Immunology, 2007
- Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myelomaBlood, 2007
- Experience with heat shock protein‐peptide complex 96 vaccine therapy in patients with indolent non‐Hodgkin lymphomaCancer, 2006
- Vaccines for tumour preventionNature Reviews Cancer, 2006
- Targeting Heat Shock Proteins for Immunotherapy in Multiple Myeloma: Generation of Myeloma-Specific CTLs Using Dendritic Cells Pulsed with Tumor-Derived gp96Clinical Cancer Research, 2005
- Interaction of Heat Shock Proteins with Peptides and Antigen Presenting Cells: Chaperoning of the Innate and Adaptive Immune ResponsesAnnual Review of Immunology, 2002
- Carboxyfluorescein succinimidyl ester‐based proliferative assays for assessment of T cell function in the diagnostic laboratoryImmunology & Cell Biology, 1999
- Priming of T cells by heat shock protein–peptide complexes as the basis of tumor vaccinesSeminars in Immunology, 1997