Vaccination of Small Cell Lung Cancer Patients with Polysialic Acid or<i>N</i>-Propionylated Polysialic Acid Conjugated to Keyhole Limpet Hemocyanin

• Lee M. Krug

  1Thoracic Oncology Service and

• Govind Ragupathi

  2Laboratory of Tumor Vaccinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, New York, and

• Kenneth K. Ng

  1Thoracic Oncology Service and

• Chandra Hood

  2Laboratory of Tumor Vaccinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, New York, and

• Harold J. Jennings

  3Institute of Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada

• Zhongwu Guo

  3Institute of Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada

• Mark G. Kris

  1Thoracic Oncology Service and

• Vincent Miller

  1Thoracic Oncology Service and

• Barbara Pizzo

  1Thoracic Oncology Service and

• Leslie Tyson

  1Thoracic Oncology Service and

• Valerie Baez

  1Thoracic Oncology Service and

• Philip O. Livingston

  2Laboratory of Tumor Vaccinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, New York, and

抄録

Purpose: Long chain polysialic acid (polySA) is a side chain on embryonal neural cell adhesion molecules that, in the adult, is largely restricted to small cell lung cancer (SCLC). Long chains of polySA are also expressed on group B meningococcus. In this clinical trial, we aimed to elicit an immune response against polysialic acid to target clinically inapparent residual disease in patients with SCLC who had successfully completed initial therapy. Experimental Design: Patients were vaccinated with either 30 μg unmodified polySA or N-propionylated-polySA (NP-polySA), conjugated to keyhole limpet hemocyanin (KLH) and mixed with 100 μg of immunological adjuvant QS-21 at weeks 1, 2, 3, 4, 8, and 16. Results: Of the 5 evaluable patients vaccinated with unmodified polySA, only 1 mounted an IgM antibody response to polySA. On the other hand, all 6 of the patients vaccinated with NP-polySA produced IgM antibodies to NP-polySA and these cross-reacted with unmodified polySA in all but 1 case. IgG antibodies to NP-polySA were observed in 5 of the patients, but these did not cross-react with polySA. The presence of IgM antibodies reactive with SCLC cell lines was confirmed in this group by flow cytometry. Complement-dependent lysis of tumor cells could not be demonstrated. However, postimmunization sera induced significant bactericidal activity against group B meningococcus when combined with rabbit complement. Conclusions: Vaccination with NP-polySA-KLH, but not polySA-KLH, resulted in a consistent high titer antibody response. We are now conducting a de-escalation dosing study with NP-polySA-KLH to better assess the immunogenicity, toxicities, and optimal dose of this vaccine. We plan to incorporate this vaccine as a component of a polyvalent vaccine with GM2, fucosylated GM1, and Globo H to target SCLC.

収録刊行物

• Clinical Cancer Research

  Clinical Cancer Research 10 (3), 916-923, 2004-02-01

  American Association for Cancer Research (AACR)

キーワード

• Cancer Research
• Oncology

詳細情報

• CRID: 1363107370489260672
• NII論文ID: 30018691794
• DOI: 10.1158/1078-0432.ccr-03-0101
• ISSN: 15573265
• ISSN: 10780432
• Web Site: https://aacrjournals.org/clincancerres/article-pdf/10/3/916/1956415/zdf00304000916.pdf
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