MALEIMIDE TUMOR ANTIGEN-CARRIER PROTEIN CONJUGATES FOR CANCER
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UCLA Technology Available For Licensing |
BACKGROUND:
Virtually all B cell malignancies express a tumor-specific immunoglobulin, whose unique variable region sequences contain antigenic determinants known as the "idiotype" (Id). The Id protein can be produced from individual patients' tumor cells by hybridoma or recombinant DNA techniques, thus yielding a patient-specific protein that can be formulated into a vaccine. To render the Id protein more recognizable by the immune system, the Id protein is usually chemically-linked to an immunogenic foreign "carrier" protein. The protein most often used for this purpose is keyhole limpet hemocyanin (KLH), the oxygen-carrying protein from a Pacific mollusk. The traditional method for linking tumor Id proteins to KLH involves glutaraldehyde. However, not all subjects immunized with glutaraldehyde Id-KLH vaccines demonstrate immune responses to the Id proteins.
INNOVATION:
Researchers at UCLA have developed a chemical method for preparing Id-KLH vaccines using maleimide. These researchers have shown the biological effectiveness of these Id-KLH vaccines synthesized by maleimide by comparing both maleimide and glutaraldehyde Id-KLH conjugates in two lymphoma model systems. The Id-KLH synthesized with maleimide demonstrated superior anti-idiotype antibody responses in vaccinated mice when compared to the glutaraldehyde derived conjugates. Moreover, these Id-KLH vaccines showed superior resistance to a lethal inoculum of tumor cells.
POTENTIAL APPLICATIONS
- Develop Id-KLH vaccines
- Therapeutic for B cell malignancy
ADVANTAGES
- Method of synthesizing Id-KLH is simple and inexpensive
- Avoids over-conjugation and destruction of critical immunogenic protein motifs
- Demonstrated superiority of maleimide Id-KLH conjugates over glutaraldehyde Id-KLH conjugates to develop more efficacious vaccines
DEVELOPMENT-TO-DATE: Id-KLH conjugates synthesized by the new chemical method have been tested in two animal tumor models, 38C13 and A20
Related Papers (Selected)
- " Hurvitz, S.A., Timmerman, J.M. 2005. Current status of therapeutic vaccines for non-Hodgkin's lymphoma. Current Opinion Oncology. 17(5): 432-40. more...
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UCLA Office of Intellectual Property
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Tel: 310-794-0558 Fax: 310-794-0638
email: ncd@research.ucla.edu
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NCD URL: http://www.research.ucla.edu/tech/ucla05-743.htm
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UCLA Technologies Available for
Licensing
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University of California.
keywords: B cell malignancy, anti-tumor, maleimide, conjugation, glutaraldehyde, Id-KLH, tumor-specific immunoglobulin therapeutics
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