Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel

• Published in: Oncology letters Vol. 12; no. 6; pp. 4493 - 4504
• Main Authors: Kyogoku, Noriaki, Ikeda, Hiroaki, Tsuchikawa, Takahiro, Abiko, Takehiro, Fujiwara, Aki, Maki, Takehiro, Yamamura, Yoshiyuki, Ichinokawa, Masaomi, Tanaka, Kimitaka, Imai, Naoko, Miyahara, Yoshihiro, Kageyama, Shinichi, Shiku, Hiroshi, Hirano, Satoshi
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.12.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: antibody response; Antigens; Cancer; Cancer vaccines; Clinical trials; Colon; Disease; Dose-response relationship (Biochemistry); Drug dosages; Esophagus; Genetic aspects; Health aspects; Immune response; immunoglobulin E; immunoglobulin G subclass; Immunoglobulins; Immunology; Liver; MAGE-A4; Melanoma; Metastasis; Oncology; Patients; Proteins; Testing; Tumor antigens; Tumors; vaccine; Vaccines; immunoglobulin G subclass; vaccine; antibody response; immunoglobulin E; MAGE-A4
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2016.5253

A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients.