Anti-synthetic Peptide Antibody Reacting at the Fusion Junction of Deletion-mutant Epidermal Growth Factor Receptors in Human Glioblastoma

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1990 Jun 1

PMID 1693434

Citations 140

Authors

P A Humphrey

A J Wong

B Vogelstein

M R Zalutsky

G N Fuller

G E Archer

H S Friedman

M M Kwatra

S H Bigner

D D Bigner

Affiliations

Soon will be listed here.

Abstract

We have investigated human gliomas that amplify and rearrange the epidermal growth factor receptor gene, with generation of an in-frame deletion mutation of 802 nucleotides in the external domain. This in-frame deletion mutation generates a local amino acid sequence at the fusion junction of what normally were distant polypeptide sequences in the intact epidermal growth factor receptor. This 14-amino acid peptide was chemically synthesized, coupled to keyhole limpet hemocyanin, and used as an immunogen in rabbits. The elicited antibody reacted specifically with the fusion peptide in ELISA. The anti-fusion junction peptide antibody was purified by passage of the antiserum over a peptide affinity column with acidic elution. The purified antibody selectively bound the glioma deletion mutant as compared to the intact epidermal growth factor receptor as assessed by immunocytochemistry, immunofluorescence, immunoprecipitation with gel electrophoresis, and binding experiments using radioiodinated antibody. These data indicate that it is feasible to generate site-specific anti-peptide antibodies that are highly selective for mutant proteins in human tumors. The anti-peptide antibody described here, and other mutation site-specific antibodies, should be ideal candidates for tumor immunoimaging and immunotherapy.

Citing Articles

CAR T cell therapy for pediatric central nervous system tumors: a review of the literature and current North American trials.

Ronsley R, Bertrand K, Song E, Timpanaro A, Choe M, Tlais D Cancer Metastasis Rev. 2024; 43(4):1205-1216.

PMID: 39251462 PMC: 11554695. DOI: 10.1007/s10555-024-10208-4.

Roles of extracellular vesicles in glioblastoma: foes, friends and informers.

Lunavat T, Nieland L, Vrijmoet A, Zargani-Piccardi A, Samaha Y, Breyne K Front Oncol. 2023; 13:1291177.

PMID: 38074665 PMC: 10704464. DOI: 10.3389/fonc.2023.1291177.

Comprehensive clinical evaluation of CAR-T cell immunotherapy for solid tumors: a path moving forward or a dead end?.

Drougkas K, Karampinos K, Karavolias I, Koumprentziotis I, Ploumaki I, Triantafyllou E J Cancer Res Clin Oncol. 2022; 149(6):2709-2734.

PMID: 36564524 PMC: 10129996. DOI: 10.1007/s00432-022-04547-4.

The IAP antagonist birinapant enhances chimeric antigen receptor T cell therapy for glioblastoma by overcoming antigen heterogeneity.

Song E, Wang X, Philipson B, Zhang Q, Thokala R, Zhang L Mol Ther Oncolytics. 2022; 27:288-304.

PMID: 36458202 PMC: 9707011. DOI: 10.1016/j.omto.2022.11.004.

Crosstalk between the B7/CD28 and EGFR pathways: Mechanisms and therapeutic opportunities.

Ren X, Li Y, Nishimura C, Zang X Genes Dis. 2022; 9(5):1181-1193.

PMID: 35873032 PMC: 9293717. DOI: 10.1016/j.gendis.2021.08.009.

References

Colapinto E, Humphrey P, Zalutsky M, Groothuis D, Friedman H, Tribolet N . Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts. Cancer Res. 1988; 48(20):5701-7. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Pullano T, Sinn E, Carney W . Characterization of monoclonal antibody R256, specific for activated ras p21 with arginine at 12, and analysis of breast carcinoma of v-Harvey-ras transgenic mouse. Oncogene. 1989; 4(8):1003-8. View

Wong A, Bigner S, Bigner D, Kinzler K, Hamilton S, Vogelstein B . Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci U S A. 1987; 84(19):6899-903. PMC: 299192. DOI: 10.1073/pnas.84.19.6899. View

Humphrey P, Wong A, Vogelstein B, Friedman H, Werner M, Bigner D . Amplification and expression of the epidermal growth factor receptor gene in human glioma xenografts. Cancer Res. 1988; 48(8):2231-8. View

Malden L, Novak U, Kaye A, Burgess A . Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. Cancer Res. 1988; 48(10):2711-4. View

Yamazaki H, Fukui Y, Ueyama Y, Tamaoki N, Kawamoto T, Taniguchi S . Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. Mol Cell Biol. 1988; 8(4):1816-20. PMC: 363345. DOI: 10.1128/mcb.8.4.1816-1820.1988. View

Kris R, Lax I, Gullick W, Waterfield M, Ullrich A, Fridkin M . Antibodies against a synthetic peptide as a probe for the kinase activity of the avian EGF receptor and v-erbB protein. Cell. 1985; 40(3):619-25. DOI: 10.1016/0092-8674(85)90210-7. View

Davis R, Czech M . Amiloride directly inhibits growth factor receptor tyrosine kinase activity. J Biol Chem. 1985; 260(4):2543-51. View

10.

Libermann T, Nusbaum H, Razon N, Kris R, Lax I, Soreq H . Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985; 313(5998):144-7. DOI: 10.1038/313144a0. View

11.

Epenetos A, Courtenay-Luck N, Pickering D, Hooker G, Durbin H, LAVENDER J . Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen. Br Med J (Clin Res Ed). 1985; 290(6480):1463-6. PMC: 1415686. DOI: 10.1136/bmj.290.6480.1463. View

12.

Gullick W, Downward J, Parker P, Whittle N, Kris R, Schlessinger J . The structure and function of the epidermal growth factor receptor studied by using antisynthetic peptide antibodies. Proc R Soc Lond B Biol Sci. 1985; 226(1242):127-34. DOI: 10.1098/rspb.1985.0087. View

13.

Gullick W, Marsden J, Whittle N, Ward B, Bobrow L, Waterfield M . Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res. 1986; 46(1):285-92. View

14.

Feramisco J, Clark R, Wong G, Arnheim N, Milley R, McCormick F . Transient reversion of ras oncogene-induced cell transformation by antibodies specific for amino acid 12 of ras protein. Nature. 1985; 314(6012):639-42. DOI: 10.1038/314639a0. View

15.

Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M . Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988; 53(4):549-54. DOI: 10.1016/0092-8674(88)90571-5. View

16.

Lee Y, Bullard D, Humphrey P, Colapinto E, Friedman H, Zalutsky M . Treatment of intracranial human glioma xenografts with 131I-labeled anti-tenascin monoclonal antibody 81C6. Cancer Res. 1988; 48(10):2904-10. View

17.

Lee Y, Bullard D, Zalutsky M, Coleman R, Wikstrand C, Friedman H . Therapeutic efficacy of antiglioma mesenchymal extracellular matrix 131I-radiolabeled murine monoclonal antibody in a human glioma xenograft model. Cancer Res. 1988; 48(3):559-66. View

18.

Sato J, Kawamoto T, Le A, Mendelsohn J, Polikoff J, Sato G . Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol Biol Med. 1983; 1(5):511-29. View

19.

Tanaka T, Slamon D, Cline M . Efficient generation of antibodies to oncoproteins by using synthetic peptide antigens. Proc Natl Acad Sci U S A. 1985; 82(10):3400-4. PMC: 397783. DOI: 10.1073/pnas.82.10.3400. View

20.

Kawamoto T, Mendelsohn J, Le A, Sato G, LAZAR C, Gill G . Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells. J Biol Chem. 1984; 259(12):7761-6. View