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Methods and compositions to generate immunity in humans against self tumor antigens by immunization with homologous foreign proteins

a technology of human immunity and homologous foreign proteins, which is applied in the direction of antibody medical ingredients, peptide/protein ingredients, instruments, etc., can solve the problems of difficult use of peptides and cancer remains one of the major causes of death

Inactive Publication Date: 2006-01-12
UNIV OF WASHINGTON
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides methods and compositions for eliciting or enhancing an immune response to a human self tumor antigen. This can be done by immunizing a human being with a foreign protein or peptide that is homologous to the antigen. The foreign protein or peptide can be in a pharmaceutically acceptable carrier or diluent, and an adjuvent can also be added. The technical effect of this invention is to provide a way to potentially treat tumors in humans by enhancing the immune response to the tumor antigen.

Problems solved by technology

Despite enormous investments of financial and human resources, cancer remains one of the major causes of death.
However, despite the presence of a detectable immune response to self tumor antigens in some patients, immunologic tolerance exists and represents a potential barrier to effectively vaccinating against tumor antigens.
Nevertheless, the use of peptides may be problematic as they are thought of as weak immunogens and HLA restriction may limit usefulness (e.g., by preventing the use of a single peptide for all patients).

Method used

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  • Methods and compositions to generate immunity in humans against self tumor antigens by immunization with homologous foreign proteins
  • Methods and compositions to generate immunity in humans against self tumor antigens by immunization with homologous foreign proteins
  • Methods and compositions to generate immunity in humans against self tumor antigens by immunization with homologous foreign proteins

Examples

Experimental program
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Effect test

example 1

HER-2 / NEU IMMUNIZATION

A. Materials and Methods

[0043] 1. Animals: Rats used in this study were Fischer strain 344 (CDF (F-344) / CrlBR) (Charles River Laboratories, Portage Mich.). Animals were maintained at the University of Washington Animal facilities under specific pathogen free conditions and routinely used for experimental studies between 3 and 4 months of age. Pathologic evaluation of rat tissues was performed by Dr. D. Liggitt, University of Washington, Department of Comparative Medicine.

[0044] 2. Neu Proteins. Rat neu protein was purified using immunoaffinity column purification techniques. Briefly, a lysate preparation of a rat neu overexpressing cell line, DHFRG8 (ATCC, Rockville Md.), was incubated overnight at 4° C. on a prepared immunoaffinity Affigel-10 column (BioRad, Hercules, Calif.). 20×107 cells were used to generate the lysate preparation (Disis et al., J. Immunol. 156:3151-3158, 1996). The Affigel-10 was coupled a rat neu specific antibody, 7.16.4 (kindly supp...

example 2

PAP IMMUNIZATION

A. Materials and Methods

[0062] 1. Recombinant rat and human PAP were expressed and purified. Recombinant rPAP was obtained from Dr. P. Vihko. rPAP was expressed in baculovirus and purified as described previously. rPAP runs as a 40 kD protein under reducing conditions on a 10-15% SDS gel (FIG. 9A). The protein readily forms dimers when not completely reduced. Recombinant hPAP for use as a homologous foreign protein in the immunization studies was also obtained from Dr. Vihko. Human PAP, expressed in baculovirus, runs as a 45 kD protein under reducing conditions (FIG. 9A) and also has a propensity to form dimers. Polyclonal rabbit anti-rPAP, elicited by immunization with a 15 aa long C-terminal peptide derived from rPAP was specific for recombinant rPAP and did not cross-react with hPAP (FIG. 9B). Polyclonal rat anti-hPAP, elicited by immunization of female Lewis rats with hPAP, cross reacted with human and rPAP (FIG. 9B).

B. Results

[0063] 1. No immunity to rPAP...

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Abstract

Methods and compositions to elicit or enhance immunity in humans against self tumor antigens are disclosed. Such immunity is generated by immunization with homologous foreign proteins. Self tumor antigens include protein expression products of overexpressed human oncogenes, such as human HER-2 / neu protein, and organ-specific or tissue-specific differentiation antigens, such as PAP or PSA, associated with tumor cells.

Description

TECHNICAL FIELD [0001] The present invention is generally directed toward generating immunity to self tumor antigens in humans. This invention is more particularly related to eliciting or enhancing immunity against human self tumor antigen by immunization with homologous foreign proteins. BACKGROUND OF THE INVENTION [0002] Despite enormous investments of financial and human resources, cancer remains one of the major causes of death. For example, cancer is the leading cause of death in women between the ages of 35 and 74. Standard approaches to treat cancer have centered around a combination of surgery, radiation and chemotherapy. Alternative approaches are needed not only to treat cancer, but also to prevent cancer. [0003] A new generation of tumor antigens has been defined: “self proteins” (J. Exp. Med. 180:1-4, 1994; Cell 82:13-17, 1995). Self tumor antigens are proteins that are expressed by both normal cells and cancer cells. (As opposed to mutated proteins that are unique and t...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/574A61K39/00A61K38/00C07K14/71
CPCA61K38/00A61K39/00A61K39/0005A61K39/0011G01N2333/82G01N33/57407G01N33/57488G01N2333/71C07K14/71A61K39/001193A61K39/001106
Inventor CHEEVER, MARTIN A.DISIS, MARY L.
Owner UNIV OF WASHINGTON