Skip to main content

Advertisement

SpringerLink
Log in

Inhibition of in vitro tumor cell growth by RP215 monoclonal antibody and antibodies raised against its anti-idiotype antibodies

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

RP215 monoclonal antibody (Mab) was shown to recognize carbohydrate-associated epitope(s) in the heavy chains of cancer cell-expressed immunoglobulins, designated in general as CA215 pan cancer marker. Growth inhibitions of tumor cells in vitro by RP215 Mab and antibodies against its anti-idiotype (anti-id) antibodies were investigated. Polyclonal rabbit anti-id antibodies and the corresponding rat anti-id Mabs were generated and characterized. Following immunizations in mice, antisera raised against anti-id antibodies were analyzed by typical immunoassays. It was observed that mouse anti-anti-id sera (Ab3) revealed binding affinity and specificity to CA215 that are comparable to those of RP215. Both RP215 and Ab3 were shown to induce apoptosis of cultured cancer cells in vitro by TUNEL and MTT assays. These experimental observations were consistent with that of in vivo tumor growth inhibition by RP215 in previous nude mouse experiments. Therefore, heterologous or homologous anti-id antibodies of RP215 that contain the internal image of its specific epitope in CA215 may serve as effective anti-cancer vaccines for therapeutic treatments of various cancers in humans. The relative stability of RP215-specific carbohydrate-associated epitope was compared to that of human IgG at extreme pH’s (≤2 or ≥12) or following NaIO4 treatments. The major molecular forms of CA215 were further documented with various enzyme immunoassays and found to have similar secondary structures to those of normal human immunoglobulin G.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

Ab2:

Anti-idiotype antibody, or anti-id antibody

Ab3:

Antibody or antiserum against anti-id antibody, or anti-anti-id antibody

Anti-id:

Anti-idiotype

DAB:

Diaminobenzidine (substrate for horse radish peroxidase)

ELISA:

Enzyme-linked immunosorbent assay, or EIA

F(ab′)2 :

Fragments obtained following pepsin digestions of immunoglobulin G

HRP:

Horse radish peroxidase

Mab:

Monoclonal antibody

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

RP215-HRP:

Horse radish peroxidase-labeled RP215 monoclonal antibody

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

References

  1. Liu H-D, Zheng H, Li M, Hu D-S, Tang M, Cao Y (2007) Upregulated expression of kappa light chain by Esptein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cells via NF-κB and AP-1 pathways. Cell Signal 19:419–427

    Article  CAS  PubMed  Google Scholar 

  2. Zheng H, Li M, Ren W, Zeng L, Liu H-D, Hu D, Deng X, Tang M, Shi Y, Gong J, Cao Y (2007) Expression and secretion of immunoglobulin alpha heavy chain with diverse VDJ recombinations by human epithelial cancer cells. Mol Immunol 44:2221–2227

    Article  CAS  PubMed  Google Scholar 

  3. Li M, Feng D-Y, Ren W, Zheng L, Zheng H, Tang M, Cao Y (2004) Expression of immunoglobulin kappa light chain constant region in abnormal human cervical epithelial cells. Int J Biochem Cell Biol 36:2250–2257

    Article  CAS  PubMed  Google Scholar 

  4. Qiu X, Zhu X, Zhang L, Mao Y, Zhang J, Hao P, Li G, Lv P, Li Z, Sun X, Wu L, Zheng J et al (2003) Human epithelial cancers secrete immunoglobulin G with unidentified specificity to promote growth and survival of tumor cells. Cancer Res 63:6488–6495

    CAS  PubMed  Google Scholar 

  5. Kimoto Y (1997) Expression of heavy-chain constant region of immunoglobulin and T-cell receptor gene transcripts in human non-hematopoietic tumor cell lines. Genes Chromosomes Cancer 22:83–86

    Article  Google Scholar 

  6. Zhu X, Li C, Sun X, Mao Y, Li G, Liu X, Zhang Y, Qiu X (2008) Immunoglobulin mRNA and protein expression in human oral epithelial tumor cells. Appl Immunohistochem Mol Morph 16:232–238

    Article  CAS  Google Scholar 

  7. Babbage G, Ottensmeier CH, Blaydes J, Stevenson FK, Sahota SS (2006) Immunoglobulin heavy chain locus events and expression of activation-induced cytidine deaminase in epithelial breast cancer cell lines. Cancer Res 66:3996–4000

    Article  CAS  PubMed  Google Scholar 

  8. Geng L-Y, Shi Z-Z, Dong Q, Cai X-H, Zhang Y-M, Cao W, Peng J-P, Fang Y-M, Zheng L, Zheng S (2007) Expression of SNC73, a transcript of the immunoglobulin α-1 gene, in human epithelial carcinomas. World J Gastroenterol 13:2305–2311

    CAS  PubMed  Google Scholar 

  9. Chen Z, Gu J (2007) Immunoglobulin G expression in carcinomas and cancer cell lines. FASEB J 21:2931–2938

    Article  PubMed  Google Scholar 

  10. Forconi F, Sahota SS, Raspadori D, Mockridge CI, Lauria F, Stevenson FK (2001) Tumor cells of hairy cell leukemia express multiple clonally related immunoglobulin isotypes via RNA splicing. Blood 98:1174–1181

    Article  CAS  PubMed  Google Scholar 

  11. Lee G, Laflamme E, Chien C-H, Ting HH (2008) Molecular identity of a pan cancer marker, CA215. Cancer Biol Ther 7:91–98

    Google Scholar 

  12. Lee G, Ge B (2009) Cancer cell expressions of immunoglobulin heavy chains with unique carbohydrate-associated biomarker. Cancer Biomarkers 5:177–188

    CAS  PubMed  Google Scholar 

  13. Lee CYG, Chen KW, Sheu FS, Tsang A, Chao KC, Ng HT (1992) Studies of a tumor associated antigens, COX-1, recognized by a Mab. Cancer Immunol Immunother 35:19–26

    Article  CAS  PubMed  Google Scholar 

  14. Lee G, Chu R-A, Ting HH (2009) Preclinical assessment of anti-cancer drugs by using RP215 Mab. Cancer Biol Ther 8:161–166

    Article  CAS  PubMed  Google Scholar 

  15. Lee G (2009) Cancer cell-expressed immunoglobulins: CA215 as a pan cancer marker and its diagnostic applications. Cancer Biomarkers 5:137–142

    CAS  PubMed  Google Scholar 

  16. Rice J, Ottensmeier CH, Stevenson FK (2008) DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer 8:108–120

    Article  CAS  PubMed  Google Scholar 

  17. Lowder JN, Meeker TC, Campbell M, Garcia CF, Gralow J, Miller RA, Warnke R, Levy R (1987) Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: correlation with clinical responses. Blood 69:199–210

    CAS  PubMed  Google Scholar 

  18. Lopez-Diaz de Cerio A, Zabalegui N, Rodriguez-Calvillo M, Inoges S, Bendandi M (2007) Anti-idiotype antibodies in cancer treatment. Oncogene 26:3594–3602

    Article  CAS  PubMed  Google Scholar 

  19. Kuo C-Y, Sun P, Lee CYG (1988) Sperm antibodies induced by anti-idiotype antibodies: a strategy in development of immunocontraceptive vaccines. J Reprod Immunol 13:193–209

    Article  CAS  PubMed  Google Scholar 

  20. Laniyu E (1986) Preparation of F(ab′)2 fragments from mouse IgG of various subclasses. In: Langone JJ, Van Vunakis H (eds) Methods in enzymology, vol 121. Academic Press, New York, pp 652–663

    Google Scholar 

  21. Losman MJ, Leung S-O, Shih LB, Shevitz J, Shukla R, Haraga L, Goldenberg DM, Hansen HJ (1995) Development and evaluation of the specificity of a rat monoclonal anti-idiotype antibody, WN, to an anti-B-cell lymphoma monoclonal anibody, LL2. Cancer Res 55:5978s–5982s

    CAS  PubMed  Google Scholar 

  22. Choi J-H, Choi K-C, Auersperg N, Leung PCK (2006) Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells. Endocr Relat Cancer 13:641–651

    Article  CAS  PubMed  Google Scholar 

  23. Chen A, Kaganovsky E, Rahimipour S, Ben-Aroya N, Okon E, Koch Y (2002) Two forms of gonadotropin-releasing hormone (GnRH) are expressed in human breast tissue and overexpressed in breast cancer: a putative mechanism for the antiproliferative effect of GnRH by down-regulation of acidic ribosomal phosphoproteins P1 and P2. Cancer Res 62:1036–1044

    CAS  PubMed  Google Scholar 

  24. Freed KA, Brennecke SP, Moses EK (2005) Gene expression of the constant region of the heavy chain of immunoglobulin G is down-regulated in human decidua in association with preeclampsia. J Reprod Immunol 68:105–120

    Article  CAS  PubMed  Google Scholar 

  25. Hong I-S, Cheung AP, Leung PCK (2008) Gonadotropin-releasing hormones I and II induce apoptosis in human granulose cells. J Clin Endocrinol Metab 93:3179–3185

    Article  CAS  PubMed  Google Scholar 

  26. Lee G, Wu Q, Li C-H, Ting H-H, Chien CH (2006) Recent studies of a new carbohydrate-associated pan cancer marker, CA215. J Clin Ligand Assay 29:47–51

    Google Scholar 

Download references

Acknowledgments

The Industry R&D Fellowship (IRDF, #360647) from NSERC (Natural Sciences and Engineering Research Council of Canada) to BG was acknowledged. This project was supported in parts by Vancouver Biotech Ltd (#080201). The NSERC and IRAP support of the following co-op students or research assistants are also acknowledged: C. Zhang, D. Tsui, E. Laflamme, A. Spreeuw and K. Huang.

Conflict of interest statement

GL is co-founder of Vancouver Biotech Ltd.

Author information

Authors and Affiliations

  1. Andrology Laboratory, UBC Center for Reproductive Health, The University of British Columbia, Rm D403A, 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada

    Gregory Lee & Bixia Ge

Authors
  1. Gregory Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bixia Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregory Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, G., Ge, B. Inhibition of in vitro tumor cell growth by RP215 monoclonal antibody and antibodies raised against its anti-idiotype antibodies. Cancer Immunol Immunother 59, 1347–1356 (2010). https://doi.org/10.1007/s00262-010-0864-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-010-0864-7

Keywords

Search

Navigation