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Innate targeting of adoptive cellular therapies

A cell and immune cell technology, applied in animal cells, allergic diseases, vertebrate cells, etc., can solve the problems of poor clinical results and other problems

Pending Publication Date: 2020-10-30
QU BIOLOGICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In contrast to the success achieved in hematologic cancers, clinical outcomes using CAR T cells in solid tumors have been dismal (see Newick et al., 2016, Oncolytic Molecular Therapy, 2016;3:16006)

Method used

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  • Innate targeting of adoptive cellular therapies
  • Innate targeting of adoptive cellular therapies
  • Innate targeting of adoptive cellular therapies

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0218] Example 1: SSI enhances the anti-tumor effectiveness of adoptively transferred tumor antigen-specific (TCR-tg) T cells

[0219] This example illustrates that site-specific immunotherapy (QBKPN SSI) of microbial PRR ligand preparations enhances adoptively transferred tumor antigen-specific CD8 + Antitumor efficacy of T cells (Pmel).

[0220] in order to achieve figure 1 Data shown, B6 mice received SSI or vehicle (30 mL SC) every other day from day -10 to day +18. On day 0, by IV injection with 3 x 10 5 Mice were challenged with B16-F10 (B16) melanoma cells. On days +2 and +6, some mice received an IP infusion of 1 mg anti-CXCR3 (clone CXCR3-173) mAb to block CXCR3-mediated chemotaxis / extravasation. On day +3, some mice were infused intravenously with 1 x 10 6 In vitro activation of CD8+Pmel(TCR-tg) cells. These activated T cells were obtained from an immunologically well-characterized mouse strain (JAX strain 005023-B6 genetic background) carrying a melanocyte / mel...

example 2

[0222] Example 2: SSI enhances antigen-specific (TCR-tg) T cells in infiltrating tumor-bearing lungs of metastatic tumors

[0223] This example illustrates site-specific immunotherapy (QBKPN SSI) of microbial PRR ligand preparations through activation of tumor antigen-specific (TCR-tg) CD8 + T cells enhanced chemoattraction and infiltration of tumor-bearing lungs.

[0224] in order to achieve figure 2 Data shown, B6 mice received SSI or vehicle (30 mL SC) every other day from day -10 to day +4. On day 0, by IV injection with 3 x 10 5 Mice were challenged with B16-F10 (B16) melanoma cells. On day +2, some mice received an IP infusion of 1 mg anti-CXCR3 (clone CXCR3-173) mAb to block CXCR3-mediated chemotaxis / extravasation. On day +3, some mice were infused intravenously with 1 x 10 6 In vitro activation of CD8+Pmel(TCR-tg) cells. On day +4, mice were sacrificed and surviving infiltrating TCR-tg T cells were counted by flow cytometry (based on Thy-mismatch labeling). and...

example 3

[0226] Example 3: SSI enhances T-cell chemokine production in tumor-bearing lungs

[0227] This example demonstrates that site-specific immunotherapy with tissue-specific microbial PRR ligand preparations can enhance chemokine production in tumor-bearing lungs late in tumor growth, when chemokines are otherwise suppressed by the tumor. This suggests that the chemokine production signature is associated with enhanced TCR-tg CD8 in SSI-treated animals + associated with T cell infiltration.

[0228] in order to achieve image 3 and Figure 4 Data shown, B6 mice received SSI (QBKPN or QBECO) or vehicle (30 mL SC) from day -10 to day +18, dosed every other day. On day 0, by IV injection with 3 x 10 5 Mice were challenged with B16-F10 (B16) melanoma cells. On day +18, mice were sacrificed and lung and serum were analyzed for chemokines by specific ELISA (not shown). As shown, QBKPN enhanced chemokine production in tumor-bearing lungs compared to vehicle and QBECO (SSI formulat...

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Abstract

Therapeutic modalities are provided for targeting adoptive cellular therapies to specific sites of disease, involving the use of specific repertoirs of PRR ligands. In effect, innate immune system signaling is provoked so as to facilitate the homing of adoptive immune cells to sites of disease, for example to the site of a solid tumor.

Description

technical field [0001] Several innovations in the field of medicine, including the treatment of cancer, involving antigen-targeted cell therapy combined with the use of tissue-specific agents containing innate immunogens such as microbial components are disclosed. Background technique [0002] In vertebrates, an important aspect of immune regulation involves the coordinated activities of the innate and adaptive immune systems. This synergistic activity involves metabolic, enzymatic, and molecular genetic changes within immune cells, orchestrating a complex system of cellular, cytokine, and chemokine communication pathways that mediate the synergistic activity of different components of these complementary systems (see Iwasaki & Madzhitov, 2015, Nature Immunology 16:343-353; WO0209748; WO03051305; Turner et al., 2014, BBA-Molecular Cell Research 1843:11 2563-2582). One aspect of this synergistic activity is the basis for ligands recognizing pattern recognition receptors (PRR...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K9/00A61P35/00A61P37/04C12N5/078C12N5/10
CPCA61K9/0019A61K9/127A61K9/1275A61K9/16A61K9/50A61P35/00A61P37/04A61K39/39A61K2039/55594C07K2319/03C07K14/7051A61K2039/82A61K2039/892A61K2039/876A61K2239/50A61K2239/55A61K2239/38A61K39/4632A61K2239/57A61K39/464402A61K2239/31A61K39/464492A61K39/4631A61K39/464468A61K39/4611A61K2300/00A61K35/17A61K39/0011A61K2039/5158A61K2039/545A61K39/02A61K2039/52
Inventor 哈罗德·大卫·格恩大卫·W·穆林斯马克·巴兹特谢尔林·卡兰
Owner QU BIOLOGICS INC
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