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 micro g unmodified polySA or N-propionylated-polySA (NP-polySA), conjugated to keyhole limpet hemocyanin (KLH) and mixed with 100 micro g 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.

• Authors: Lee M Krug, Govind Ragupathi, Kenneth K Ng, Chandra Hood, Harold J Jennings, Zhongwu Guo, Mark G Kris, Vincent Miller, Barbara Pizzo, Leslie Tyson, Valerie Baez, Philip O Livingston
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 3 Pg. 916-23 (Feb 01 2004) ISSN: 1078-0432 [Print] United States
• PMID: 14871967 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Antigens, Tumor-Associated, Carbohydrate
• Cancer Vaccines
• Globo-H
• Immunoglobulin G
• Immunoglobulin M
• Saponins
• Sialic Acids
• Vaccines, Conjugate
• globo H-keyhole limpet hemocyanin QS-21 vaccine
• polysialic acid
• G(M2) Ganglioside
• G(M1) Ganglioside
• saponin QA-21V1
• Complement System Proteins
• Hemocyanins
• keyhole-limpet hemocyanin

Topics

• Adjuvants, Immunologic (pharmacology)
• Aged
• Antigens, Tumor-Associated, Carbohydrate (metabolism)
• Cancer Vaccines (therapeutic use)
• Carbohydrate Sequence
• Carcinoma, Small Cell (therapy)
• Complement System Proteins
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• G(M1) Ganglioside (metabolism)
• G(M2) Ganglioside (metabolism)
• Hemocyanins (therapeutic use)
• Humans
• Immunoglobulin G (chemistry)
• Immunoglobulin M (chemistry)
• Immunotherapy (methods)
• Lung Neoplasms (therapy)
• Male
• Middle Aged
• Models, Chemical
• Molecular Sequence Data
• Saponins (pharmacology)
• Sialic Acids (therapeutic use)
• Time Factors
• Vaccines, Conjugate (therapeutic use)