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Cancer Vaccines and Therapeutic Methods

Inactive Publication Date: 2009-08-27
THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018]The present invention is also related to a method of identifying a tumor associated antigen by providing a recipient cell and an immunogenic cell capable of inducing an immune response to a tumor cell and comparing nucleic acid of the recipient cell and the immunogenic cell and identifying the nucleic acid with increased expression in the immunogenic cell as the nucleic acid encoding for a tumor associate

Problems solved by technology

For some types of cancers and stages of disease at diagnosis, morbidity and mortality rates have not improved significantly in recent years in spite of extensive research.
One possible explanation is that even though the immune system can adversely affect diffuse and smaller tumors, it cannot effectively destroy large, established neoplasms.
However, the direct modification of cancer cells from a primary neoplasm is technically challenging.
It requires the establishment of a tumor cell line, which cannot always be accomplished.

Method used

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  • Cancer Vaccines and Therapeutic Methods
  • Cancer Vaccines and Therapeutic Methods
  • Cancer Vaccines and Therapeutic Methods

Examples

Experimental program
Comparison scheme
Effect test

example 1

Cytokine-Secretion by LM Mouse Fibroblasts

[0096]Among other advantages, the use of a fibroblast cell line as the recipient of genomic DNA from the breast cancer cells enables the recipient cells to be modified in advance of DNA-transfer to augment their nonspecific immunogenic properties. In this instance, the fibroblasts were modified to secrete IL-2 and to express allogeneic MHC class I-determinants. IL-2 is a growth and maturation factor for CTLs.

[0097]A replication-defective retroviral vector (pZipNeoSVIL-2) was used to modify the fibroblasts used as DNA-recipients to secrete IL-2 (pZipNeoSV-IL-2; from M.K.L. Collins, University College, London, England) specifying human IL-2 was used for this purpose. The IL-2-specifying vector was packaged in GP-1-env AM 12 cells (from A. Bank, Columbia University, New York, N.Y.). The vector also included a neor gene under control of the Moloney leukemia virus long terminal repeat. The neor gene conferred resistance to the aminoglycoside anti...

example 2

Modification of the Cytokine-Secreting Fibroblasts to Express H-2Kb-Class I-Determinants

[0100]Allogeneic class I-determinants are strong immune adjuvants (Conte P F, Cancer 2004; 101:704-12; Hammerling G J, J Immunogen 1986; 13:15-157; Hui K M, J Immunol 1989; 143:3835-43; Ostrand-Rosenberg S, J Immunol 1990; 144:4068-71). To further augment their immunogenic properties, the fibroblasts were modified to express MHC H-2Kb-determinants, allogeneic in C3H / He mice. A plasmid (pBR327H-2Kb) (Biogen Research Corp., Cambridge, Mass.) encoding H-2Kb-determinants was used. Ten g of pBR327H-2Kb and 1 g of pBabePuro (from M. K. L. Collins), a plasmid specifying a gene that confers resistance to puromycin, were mixed with Lipofectin (Gibco BRL), and added to 1×106 cytokine-secreting fibroblasts in 10 ml of DMEM, without FBS. (A 10:1 ratio of tumor-DNA to plasmid DNA was used to increase the likelihood that cells converted to puromycin-resistance took up tumor-DNA as well.)

[0101]The IL-2-secretin...

example 3

Paclitaxel Inhibited the Growth of Breast Cancer Cells in C3H / He Mice

[0106]Paclitaxel is a potent inhibitor of cell division (Ross J L, Proc Natl Acad Sci (USA) 2004; 101:12910-5; Nettles J H, Science 2004; 305:866-9; Gaitanos T N, Cancer Res 2004; 64:5063-7). It blocks cells in the G2 / M phase of replication through its effect on the formation and function of microtubules within the cell. To determine if paclitaxel affected the growth of the breast cancer cells used in the experiments described here, naïve C3H / He mice were injected into the fat pad of the breast with 1×105 of the malignant cells (SB5b cells). Six days after injection of the cancer cells, the mice received a single i.p. injection of varying amounts of paclitaxel (range=05 to 2.25 mg / kg). The effect of paclitaxel on the growth of SB5b cells was determined by measurements of tumor volume at varying times afterward (FIG. 1).

[0107]Mean tumor volumes were determined by the equation 0.5 l×w2 where l=length and w=width. The...

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Abstract

Compositions and methods of producing improved cancer vaccines are described. In addition, methods of identifying tumor associated antigens are also described.

Description

PRIORITY CLAIM[0001]This application claims priority from U.S. provisional patent applications 60 / 665,985 filed Mar. 29, 2005; 60 / 697,334 filed Jul. 7, 2005; and 60 / 733,663 filed Nov. 4, 2005; the disclosures of which are incorporated herein in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT[0002]This invention was made in part with Government support under Grant Number R01-DEO13970-01A2 awarded by the National Institute of Dental and Craniofacial Research (NIDCR). The Government has certain rights in this inventionFIELD OF THE INVENTION[0003]The present invention relates to vaccines and methods for treating a disease, such as cancer. More specifically, the present invention relates to immunogenic cells which act to stimulate and induce an immunogenic response to an antigen, such as a tumor associate antigen (TAA).[0004]The present invention also concerns treatment of cancer using a genomic DNA-based vaccine. In addition, the present invention concern...

Claims

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Application Information

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IPC IPC(8): A61K35/12C12N5/00C12Q1/02C12Q1/68A61P35/00A61K39/00
CPCA61K35/12A61K38/193A61K2039/55527A61K2039/55522A61K2039/53A61K2039/5156A61K2039/5154A61K48/00A61K39/39A61K39/0011A61K38/208A61K38/2013A61K38/2026A61K38/204A61K2300/00A61P35/00A61K2239/49A61K39/4622A61K39/46447A61K39/464499A61K39/464406A61K39/4615
Inventor COHEN, EDWARD P.
Owner THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS