Maleimide Tumor Antigen-carrier Protein Conjugates for Cancer
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
Develop Id-KLH vaccinesTherapeutic for B cell malignancy
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.
Patent Number: US8575319B2
Application Number: US2008281229A
Inventor: Timmerman, John M.
Priority Date: 10 Mar 2006
Priority Number: US8575319B2
Application Date: 29 Aug 2008
Publication Date: 5 Nov 2013
IPC Current: C07K001600
US Class: 5303911 | 4241781
Assignee Applicant: The Regents of the University of California
Title: Cleavable vaccine compositions and uses thereof and methods of making and using the same
Usefulness: Cleavable vaccine compositions and uses thereof and methods of making and using the same
Summary: The methods are useful for making a vaccine and for treating B cell proliferative disease or a T cell proliferative disease. The B-cell proliferative disease is B-cell lymphoma, leukemia, multiple myeloma, or light chain amyloidosis (all claimed).
Novelty: Making vaccine for treating B cell proliferative disease by conjugating a linker to an immunogenic carrier and a protein antigen for forming covalent bond that is cleavable under lysosomal processing conditions
Disease Diagnostic/Treatment
Cancer/Tumor
8575319
State of Development Id-KLH conjugates synthesized by the new chemical method have been tested in two animal tumor models, 38C13 and A20 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. Related Materials Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines. Mol Immunol. (2009) Tech ID/UC Case 20290/2005-743-0 Related Cases 2005-743-0
Current status of therapeutic vaccines for non-Hodgkin's lymphoma. Curr Opin Oncol. (2005)
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