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A Nanoparticle Based Platform for Immunomonitoring upon Vaccination
P. Daftarian, V. Lemmon, A. Kaifer, R. Chowdhury
 
Problem
Currently, there are no methods of establishing a vaccine efficacy (immune response upon vaccination) for individual patient.
 
Solution
Accurate measurement of the immune response is an indicator of success of a therapeutic or prophylactic intervention and is of paramount importance in evaluation of (cancer) vaccine efficacy. Universal reproducibility, accuracy and precision of immune cell based assays for immune monitoring of any therapeutic agent is a challenge recognized widely in ongoing clinical trial evaluations. Major limitations include, the lack of accurate immunomonitoring methods of cellular immune responses, the lack of consensus on the method of choice, poor reproducibility, high cost, low correlation with protection and the requirement for specialized skills and instrumentation. Indeed, peptide cocktails commonly used for immunomonitory of cell mediated immunity may not be an accurate representation of forms seen in vivo during infection. We have described a non toxic, targeted nanoparticle-based method for transfection of APCs in human peripheral blood mononuclear cells (PBMC) for rapid, low cost generation of properly configured pathogen epitopes with generalizable applicability for accurate monitoring of cellular immunity. The nanoparticle used is composed of PADRE-derivatized dendrimer. Our approach will feature the use of PADRE-derivatized-dendrimers which specifically bind to MHC class II molecules expressed on APC to deliver specific epitopes of the infectious agent to target cells.
 
Competitive Advantage
Unlike current methods for immunomonitoring, this platform not only solves the HLA compatibility but also negates the need for cocktail of epitopes. The transfected cells can be prepared using plasmid containing gene encoding for the protein used in a vaccine ahead of time, and frozen viably in multiple aliquots for subsequent use as autologous APC when co-cultured with PBMC from the same individual.
 
Applications
This technology can be used to prepare a vaccine efficacy testing product.
 
Patent Status
A PCT patent application was filed May 19, 2010.
 
Licensing Opportunity
We are seeking a commercialization partner with capabilities in product development, sales, and marketing. An exclusive license is available.
 
Selected References
Pirouz Daftarian, Genetic Vaccines and immunoevaluation of humoral and CTL responses. In Vaccines, Immunity, and Well-Being, to be held May 17-19, 2009, at The Gateway Hotel, Ames, Iowa. http://www.nwrc.iastate.edu/symposia/program.pdf

Pirouz Daftarian et al., Improved Protein-Free Methods for the Generation and Screening of Monoclonal Antibodies: Use of Nucleic Acid-Based Delivery and Rapid HTP Infrared-Based Assay. Meeting the Challenge of Delivery, Safety and Efficacy. Pal Talk 2009, San Diego, Ca. http://www.chi-peptalk.com/ptt.asp. http://www.infoshop-japan.com/conference/peptalk09/nab_day1.shtml

Marc Mansour, Bill Pohajdak, W Martin Kast, Antar Fuentes-Ortega, Ella Korets-Smith, Genevieve M Weir, Robert G Brown, and Pirouz Daftarian. Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMaxᆴ. Journal of Translational Medicine 2007, 5:20.

Pirouz Daftarian, Marc Mansour, Bill Pohajdak, Antar Fuentes-Ortega, Ella Korets-Smith, Lisa MacDonald, Genevieve Weir, Robert G. Brown, and W. Martin Kast. . Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMaxᆴ encapsulated CTL/T helper peptides. Journal of Translational Medicine 2007, 5:26.

Guang-Yun Song,..Pirouz Daftarian, Zhongde Wang, Don Diamond and Joshua D. I. Ellenhorn. An MVA vaccine overcomes tolerance to human p53 in mice and humans. Cancer Immunology, Immunotherapy. 2007, 56:11931205

Pirouz Daftarian., &and W. Martin Kast. Eradication of established HPV 16-expressing tumors by a single administration of a vaccine composed of a liposome-encapsulated CTL-T helper fusion peptide in a water-in-oil emulsion. Vaccine, 2006, 24: 5235-5244.

Daftarian, Pirouz; Mansour, Marc; Fuentes-Ortega, Antar; Korets-Smitha, Ella; Brown, Robert G.; Martin Kast, W; Pohajdak, Bill. Treatment of Melanoma by the Simultaneous Administration of CTL T-Helper Epitope-Containing Peptides From P53 And Trp-2 in Vaccimax. Journal of Immunotherapy: 2006 - Volume 29 - Issue 6 - p 646

Pirouz Daftarian, et. al. Nucleotides-Based Immunization: Comparison of Water-In-Oil Liposome-Based Delivery of Nucleotides with in vivo Electroporation. The 23rd Annual Meeting of the International Society for Biological Therapy of Cancer (iSBTc), NOV. 2008.

Pirouz Daftarian, &and Don J. Diamond. Novel Epitope Peptide Fusions Conjugated with CpG ssODN Confer Enhanced Immunogenicity and HIV Recognition. Vaccine 2005; 23:3453-68.

Pirouz Daftarian, ..and Joshua D.I. Ellenhorn. Two Distinct Pathways of Immuno-modulation Improve Potency of p53 Immunization in Rejecting Established Tumors. Cancer Research, 2004, 64: 5407.

Pirouz Daftarian, ..and Don J. Diamond. Immunization with T H-CTL Fusion Peptide and CpG DNA in Transgenic HLA A2 Mice Induces Recognition of HIV-infected T Cells and Clears a Recombinant Vaccinia Virus Challenge. Journal of Immunology, 2003, 171(8). Zhongde Wang, ..P. Daftarian, W.J. Britt, and Don J. Diamond. Recombinant MVA Expressing a Soluble form of Glycoprotein B Causes Durable Immunty and Neutralizing Antibodies Against Multiple Strains of CMV. Joural of Virology. 2004; 78(8): 39653976.

Daftarian P, et al. In vitro and in vivo bile duct cell immune injury in citrobacter induced murine colitis: a model for primary sclerosing cholangitis. The Canadian Journal of Gastrology October 2002.

A. Kumar, J. M. P. Daftarian, D. W. Cameron,L. Fillion & F. Diaz-Mitoma. Dysregulation of B7.2 (CD86) expression on monocytes of HIV-infected individuals is associated with altered production of IL-2 Clin Exp Immunol 1999, 117(84-92).

A. Kumar, JB Angel, M.P. Daftarian, K. Parato, LG Filion, D. Cameron, Diaz-Mitoma F. Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness. Clin Exp Immunol 1998, 114(78-86).

Angel JB, Daftarian P, ... Improvement in cell-mediated immune function during potent anti-human immunodeficiency virus therapy with ritonavir plus saquinavir. J Infect Dis 1998 Apr 177:4 898-904.

M. Pirouz Daftarian, .., F. Diaz-Mitoma. 1996. IL-10 Production is Enhanced in T cells by IL-12 and IL-6 and in Monocytes by Tumor Necrosis Factor-a . J. Immunol. 157:12-20.

M.P. Daftarian, F... A. Kumar. 1995. Dysregulated Production of Interleukin (IL)-10 And IL-12 By Peripheral Blood Lymphocytes From HIV Infected Individuals Is Associated With Altered Proliferative Responses To Recall Antigens. Clin. Diag. Lab. Immunol. 2:712-718.

F. Diaz-Mitoma, A&, M.P. Daftarian, L.G. Fillion, and W. Cameron. 1995. Up- Regulation Of Interleukin-10 And Its Reciprocal Expression With Interferon-g In Peripheral Lymphocytes From HIV-Seropositive Patients. Clin. & Exp. Immunol. 102:31-39.
 
 

 

 

 

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