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Immune system modulators

a technology of immune system and modulator, which is applied in the field of immune system modulators to achieve the effects of enhanced expression, enhanced cytotoxicity, cell migration, and/or cell proliferation, and enhanced cytotoxicity

Inactive Publication Date: 2019-12-12
CANIMGUIDE THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes methods of inhibiting the binding of human albumin or fragments to certain receptors on immune cells. This can be accomplished by providing a polynucleotide or vector that encodes an inhibitor of these peptides. The methods can involve detecting the inhibition or activation of immune cells based on various criteria such as CD55 or CD71 expression, cytokine production, cell migration, and cell proliferation. Additionally, the patent suggests co-administering therapeutic agents that can further stimulate the immune cells. Overall, the patent offers a potential for developing new treatments for immune-related diseases by targeting the binding of albumin to certain receptors on immune cells.

Problems solved by technology

For example, antibodies and peptides that bind to the albumin-derived immunoregulatory peptides or structures were made and these inhibitors of albumin-derived immunoregulatory peptides or structures were found to interfere with the ability of the albumin-derived immunoregulatory peptides or structures to inhibit or suppress immune cell function.

Method used

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Examples

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example 1

tides with Immune Inhibitory Activities

[0734]Identification of Immunoregulatory Peptides

[0735]An artificial cell surface (ACS) was prepared by selectively biotinylating cell surface structures of PBMCs and after lysing the cells binding the biotinylated proteins to streptavidin columns (see Example 17 for further description of the ACS). The mixture of peptides obtained after trypsination was adsorbed by ACS and the binding peptides were identified by comparing adsorbed and unabsorbed peptide solutions using the MALDI TOF ms technique. Based on their degree of binding and their spatial relation to previously identified immunoregulatory structures, four new peptides were selected to be synthesized and investigated for their immunoregulatory activity, primarily the effect on the proliferative response to IL-2. One of these peptides, P3028 (SEQ ID NO: 185) was found to have multiple immunoinhibitory activities.

[0736]Expression of the P3028 Epitope in Malignant Tumors

[0737]Rabbit polycl...

example 2

ACS-Identified Peptides on IL-2 Induced Proliferation

[0743]Human Ex Vivo Model for Immunosuppression in Cancer Patients

[0744]Interleukin-2 (IL-2) plays a major role in initiation and activation of an immune response and its capacity to induce lymphokine activated killer cells (LAK-cells), T-cell proliferation and cytotoxicity. Accordingly, a human ex vivo model of IL-2 stimulation of immune cells was developed. This model was useful for studying the effects of immune system modulators, such as P3028, and inhibitors thereof.

[0745]The model included PBMCs isolated from venous blood samples from healthy blood donors (control samples) or cancer patients. One hundred pI of culture medium (RPMI 1640 Dutch's modification (Gibco, InVitrogenAB, Stockholm, Sweden) supplemented with 200 IV / ml penicillin, 200 ug / ml streptomycin, 4 mM L-glutamine (all from Sigma Chemical Co. MO, US) and 20% heat-inactivated human serum) were added to roundbottomed, 96-well tissue culture plates (Costar, Corning ...

example 3

P3028 on T-Cell Receptor Stimulation

[0753]To examine the effects of P3028 on T cell receptor stimulation, Blood for PBMC isolation was provided from healthy control samples in 50 ml transfusion bags with acid dextrose citrate solution A. Whole blood was diluted 1:1 in PBS containing 2 mM EDTA. PBMCs were then isolated by Ficoll-paque Plus (GE Healthcare Bio-Sciences AB, Sweden) density gradient centrifugation after which the cells were washed first in PBS with 2 mM EDTA and second in lymphocyte culture media. Cell viability was assessed by exclusion of 0.02% Trypan Blue and was always above 95%. The cell suspension was counted in a haemocytometer. PBMCs were suspended in the culture medium without sera and the cell concentration adjusted to 1×106 lymphocytes / ml for proliferation assays and 6.4×105 for migration assays respectively. The lymphocyte culture medium RPMI 1640 (Invitrogen, Sweden) was complemented with 1% Penicillin / Streptomycin (Invitrogen, Sweden) and 4 mM Gluta-Max (In...

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Abstract

The present invention described herein relates to compositions that interact with molecules that suppress the immune system. More specifically, embodiments described herein concern the discovery, manufacture, and use of compositions that remove immunosuppression the immune system by binding to immunoregulatory peptides that interact with receptors on immune cells, compositions the can stimulate immune cells, and compositions that are cytotoxic to tumor cells.

Description

RELATED APPLICATIONS[0001]This application is a divisional of U.S. patent application Ser. No. 15 / 488,283 filed Apr. 14, 2017, now U.S. patent Ser. No. 10 / 301,356, which is a continuation of U.S. patent application Ser. No. 14 / 916,512 filed Mar. 3, 2016, now U.S. Pat. No. 9,657,059, which is a U.S. National Phase of PCT International App. No. PCT / US2014 / 054612, filed on Sep. 8, 2014, designating the United States of America and published in the English language, which claims the benefit of U.S. Provisional Application Ser. No. 61 / 875,598, filed Sep. 9, 2013, each of which is hereby incorporated by reference in its entirety.SEQUENCE IN ELECTRONIC FORMAT[0002]The present application is being filed along with a Sequence Listing as an ASCII text file via EFS-Web. The Sequence Listing is provided as a file entitled CANIG005WO.TXT, created and last saved on Sep. 8, 2014, which is 162,189 bytes in size, and updated by a file entitled CANIG005D1SEQUENCE.TXT, created and last saved on Aug. 1...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K7/06C07K14/705C07K14/715C07K14/76C07K7/08
CPCA61K38/00C07K7/08C07K14/70546C07K7/06C07K14/7155C07K14/76C07K2319/00A61P35/00
Inventor HÅKANSSON, LEIF
Owner CANIMGUIDE THERAPEUTICS