Multiple myeloma remains essentially an incurable disease despite modern chemotherapy ana Done marrow stem cell transplantation. Immunotherapy is an attractive approach in multiple myeloma since it is more specific, less toxic and possesses memory that could provide long-term immunosurveillance to reduce disease relapse following stem cell transplantation. However, there is at present a general lack of suitable- candidate antigens for this purpose. The idiotypic protein (Id) produced by myeloma cells is clone specific and has been used for immunotherapy. Unfortunately Id is a very weak antigen. Although Id-specific immune responses have been successfully induced in patients by vaccination of Id, the immune responses were generally weak and the associated antitumor responses sub-optimal. We hypothesize that, in addition to Id, myeloma cells express other novel and unique antigens that may be suitable for immune targeting. Identification of these antigens forms the basis for future design of potent polyvalent tumor vaccines for multiple myeloma. We have recently applied the serological screening of expression cDNA library (SEREX) technology to multiple myeloma and have isolated 24 clones reactive with high titer IgG in the autologous serum. In this proposal, we will characterize these clones molecularly and immunologically. We will obtain the full-length sequences of these 24 clones, carry out -sequence homology search and mutational studies, determine the prevalence of expression of the transcripts and antibodies in myeloma patients and generate recombinant proteins for novel sequences to study the ability of these gene products to elicit potentially beneficial antitumor immune responses. Successful completion of this project will form the basis for the rational design of polyvalent vaccines for multiple myeloma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA088434-05
Application #
6574745
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Yovandich, Jason L
Project Start
2000-04-01
Project End
2003-03-31
Budget Start
2002-04-05
Budget End
2003-03-31
Support Year
5
Fiscal Year
2002
Total Cost
$228,202
Indirect Cost
Name
Texas Tech University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
609980727
City
Lubbock
State
TX
Country
United States
Zip Code
79430
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Ahmed, Sharif Uddin; Meklat, Farouk; Shahriar, Masum et al. (2009) SEMG-1 expression in early stage chronic lymphocytic leukemia. Cytotherapy 11:238-44
Meklat, Farouk; Zhang, Yana; Shahriar, Masum et al. (2009) Identification of protamine 1 as a novel cancer-testis antigen in early chronic lymphocytic leukaemia. Br J Haematol 144:660-6
Zhang, Yana; Shahriar, Masum; Zhang, Jian et al. (2009) Clofarabine induces hypomethylation of DNA and expression of Cancer-Testis antigens. Leuk Res 33:1678-83
Tabaczewski, Piotr; Nadesan, Suhasini; Lim, Seah H (2009) Early renal arterial stent thrombosis associated with the JAK2 V617F mutation. Leuk Res 33:573-4
Tabaczewski, Piotr; Nadesan, Sushani; Lim, Seah H (2009) Zap-70 positive chronic lymphocytic leukemia co-existing with Jak 2 V671F positive essential thrombocythemia: a common defective stem cell? Leuk Res 33:854-5
Zhang, Yana; Wang, Zhiqing; Zhang, Jian et al. (2008) Semenogelin I expression in myeloma cells can be upregulated pharmacologically. Leuk Res 32:1889-94
Li, Zhanfei; Li, Wei; Meklat, Farouk et al. (2007) A yeast two-hybrid system using Sp17 identified Ropporin as a novel cancer-testis antigen in hematologic malignancies. Int J Cancer 121:1507-11
Meklat, Farouk; Li, Zhanfei; Wang, Zhiqing et al. (2007) Cancer-testis antigens in haematological malignancies. Br J Haematol 136:769-76
Rohrer, James E; Lim, Seah H; Bock, Frank Andrew (2007) Medical condition is related to treatment preference in cancer patients: implications for quality assessment. Am J Hosp Palliat Care 24:36-41

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