Efficient In vivo Priming by Vaccination with Recombinant NY-ESO-1 Protein and CpG in Antigen Naïve Prostate Cancer Patients

• Published in: Clinical cancer research Vol. 17; no. 4; pp. 861 - 870
• Main Authors: KARBACH, Julia, NEUMANN, Antje, JÄGER, Elke, ATMACA, Akin, WAHLE, Claudia, BRAND, Kathrin, VON BOEHMER, Lotta, KNUTH, Alexander, BENDER, Armin, RITTER, Gerd, OLD, Lloyd J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.02.2011
• Subjects: Adaptive Immunity; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Antigens, Neoplasm - administration & dosage; Antigens, Neoplasm - adverse effects; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Chemotherapy, Adjuvant; Gynecology. Andrology. Obstetrics; Humans; Injections, Intradermal; Male; Male genital diseases; Medical sciences; Membrane Proteins - administration & dosage; Membrane Proteins - adverse effects; Membrane Proteins - immunology; Nephrology. Urinary tract diseases; Oligodeoxyribonucleotides - administration & dosage; Oligodeoxyribonucleotides - adverse effects; Oligodeoxyribonucleotides - immunology; Pharmacology. Drug treatments; Prostatic Neoplasms - immunology; Prostatic Neoplasms - therapy; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Human; Urinary system disease; Prostate disease; Tumor associated antigen; Nucleotide sequence; Vaccination; Patient; Priming; Malignant tumor; Prevention; In vivo; GC rich sequence; Recombinant protein; Male genital diseases; Prostate cancer; Cancer; NYESO1 antigen
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-10-1811

NY-ESO-1, one of the most immunogenic tumor antigens, is expressed in 15% to 25% of metastatic prostate cancers. The immunological and clinical effects of vaccination with recombinant NY-ESO-1 protein combined with CpG as adjuvant were evaluated. In a phase I clinical study, patients with advanced prostate cancer were vaccinated with recombinant NY-ESO-1 protein (100 μg) mixed with CpG 7909 (2.5 mg) every 3 weeks intradermally for 4 doses. Objectives of the study were the safety of the vaccine and changes of specific humoral and cellular immunological responses to NY-ESO-1 in relation to detectable NY-ESO-1 expression in the individual tumor. All 12 baseline sero-negative patients developed high-titer NY-ESO-1 antibody responses. B-cell epitope mapping identified NY-ESO-1 p91-110 to be recognized most frequently by vaccine-induced antibodies. Two patients developed significant antibody titers against the adjuvant CpG. NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were induced in 9 patients (69%). Five of these 9 patients did not express NY-ESO-1 in the autologous tumor. Postvaccine CD8+ T-cell clones recognized and lyzed HLA-matched tumor cell lines in an antigen-specific manner. Our data provide clear evidence for the capacity of NY-ESO-1 protein/CpG vaccine to induce integrated antigen-specific immune responses in vivo and to efficiently prime CD8+ T-cell responses in NY-ESO-1 antigen-negative patients. Our results may also support further clinical vaccination protocols with NY-ESO-1 protein not only focused on the treatment of existing cancer, but also to prevent further development of NY-ESO-1 positive cancers in vivo.