Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin Journal Article

Authors: Krug, L. M.; Ragupathi, G.; Ng, K. K.; Hood, C.; Jennings, H. J.; Guo, Z.; Kris, M. G.; Miller, V.; Pizzo, B.; Tyson, L.; Baez, V.; Livingston, P. O.
Article Title: Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin
Abstract: 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.
Keywords: adult; clinical article; aged; middle aged; unclassified drug; clinical trial; fatigue; cisplatin; flow cytometry; anorexia; carboplatin; etoposide; nausea; lung neoplasms; peripheral neuropathy; drug synthesis; time factors; coughing; fever; lung small cell cancer; immune response; molecular sequence data; immunotherapy; immunoglobulin g; cancer vaccine; cancer vaccines; immunogenicity; antibody response; vaccination; polysialic acid; tumor cell; cytolysis; immunological adjuvant; flu like syndrome; headache; enzyme-linked immunosorbent assay; cross reaction; adjuvants, immunologic; models, chemical; immunoglobulin g antibody; antigens, tumor-associated, carbohydrate; carbohydrate sequence; antibody production; antibody titer; sialic acids; cell adhesion molecule; complement; immunoglobulin m antibody; hemocyanin; immunoglobulin m; saponins; vaccines, conjugate; carcinoma, small cell; qs 21; bactericidal activity; neisseria meningitidis; g(m2) ganglioside; complement system proteins; g(m1) ganglioside; injection pain; humans; human; male; female; priority journal; article; n propionylated polysialic acid
Journal Title: Clinical Cancer Research
Volume: 10
Issue: 3
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2004-02-01
Start Page: 916
End Page: 923
Language: English
DOI: 10.1158/1078-0432.ccr-03-0101
PROVIDER: scopus
PUBMED: 14871967
Notes: Clin. Cancer Res. -- Cited By (since 1996):61 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Source: Scopus
Altmetric Score
MSK Authors
  1. Kenneth K Ng
    36 Ng
  2. Lee M Krug
    211 Krug
  3. Govindaswami Ragupathi
    133 Ragupathi
  4. Vincent Miller
    259 Miller
  5. Mark Kris
    597 Kris
  6. Leslie Tyson
    50 Tyson
  7. Barbara Pizzo
    31 Pizzo
  8. Chandra Hood
    14 Hood
  9. Valerie J Baez
    4 Baez