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Compositions and methods for inducing humoral and cellular immunities against tumors and cancer

A composition and cancer technology, applied in chemical instruments and methods, drug combinations, anti-tumor drugs, etc., can solve problems such as weak immunogenicity and shrinking immune response specificity

Pending Publication Date: 2020-04-21
癌症进展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Peptide vaccines have the potential advantage of narrowing the specificity of the immune response, but they can sometimes have the disadvantage of eliciting weak immunogenicity

Method used

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  • Compositions and methods for inducing humoral and cellular immunities against tumors and cancer
  • Compositions and methods for inducing humoral and cellular immunities against tumors and cancer
  • Compositions and methods for inducing humoral and cellular immunities against tumors and cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0258] Tumor generation in mice

[0259] To determine whether PAS treatment induces both humoral and cellular immune responses and confers a synergistic effect on immune checkpoint antibody therapy, 5 x 10 5 A solution of 0.1 ml of murine mT3 pancreatic cancer cells in PBS is introduced subcutaneously into the flank to generate tumors in immunocompetent mice (eg, C57BL / 6 mice that are syngeneic for murine mT3 pancreatic cancer cells). One week after tumor formation, mice were treated with PAS and one or more immune checkpoint inhibitors, such as figure 1 shown.

[0260] Treatment of animals was initiated one week after mT3 pancreatic cancer cell inoculation, as this time frame ensured that all animals in the study had palpable subcutaneous tumors and that the treatment did not interfere with tumor initiation. The primary endpoints were tumor growth and survival. Tumor growth was measured weekly with calipers and the volume of the tumor was calculated as L x W 2 x 0.5. ...

Embodiment 2

[0269] T in terminally differentiated CD3 EMRA CD4 – / CD8 – analysis of cells

[0270] T cell subsets

[0271] Tumors were induced in mice as described in Example 1. T lymphocytes were isolated from splenic peripheral blood mononuclear cells (PBMCs) isolated from mice treated with PBS, PD-1Ab, PAS100, or PAS100+PD-1Ab. Various subsets of T cells were identified by flow cytometry using the antibodies listed in Table 1. In particular, the first T cell subset, the CD3 + / CD4 – / CD8 – , and from this subset were then isolated representative CD3 + / CD4 – / CD8 – / CD44 – / CD62L – the T EMRA Another subpopulation of cells. The percentages and ratios of these various subpopulations present in mice that had been treated with PBS, PD-1Ab, PAS100, or PAS100+PD-1Ab have been determined and the results are shown in Figure 3A and Figure 3B middle.

[0272] Figure 3A CD3 in mice treated with PBS, PD-1Ab, PAS100 or PAS100 / PD-1 is shown + T in T cells EMRA cells (C...

Embodiment 3

[0275] Cytokine Activation Assay for PAS100

[0276] T lymphocytes were isolated from splenic peripheral blood mononuclear cells (PBMCs) isolated from mice treated with PAS100. These cells were evaluated by flow cytometry to determine whether they were indeed T cells activated by the cytokines activating interferon-gamma (INFG), granzyme-B (granzyme), perforin, and tumor necrosis factor-alpha (TNFα). cell. result in Figure 4A and Figure 4B available in .

[0277] Figure 4A showed that T cells isolated from mice treated with PAS100 were indeed activated. When these same cells were restimulated in culture with gastrin for 6 hours (see Figure 4B ), they were re-stimulated and released more cytokines, confirming immunization of PAS100-stimulated T cells and further confirming that these T cells specifically responded to gastrin.

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Abstract

Provided are methods for sensitizing gastrin-associated tumors and / or cancers in subjects to inducers of humoral and cellular immune responses. In some embodiments, the methods relate to administeringcompositions that have anti-gastrin antibodies, gastrin peptides, and / or nucleic acids that inhibit expression of gastrin gene products to subjects. Also provided are methods for preventing, reducing, and / or eliminating the formation of fibroses associated with tumors and / or cancers, and methods for treating gastrin-associated tumors and / or cancers that include administering to subjects in need thereof a first agent that provides and / or induces an anti-gastrin humoral or cellular immune response in the subject and a second agent that includes one or more stimulators of cellular immune responses against the tumors and / or cancers.

Description

[0001] References to related applications [0002] This application claims the benefit of U.S. Provisional Patent Application Serial No. 62 / 520,267, filed June 15, 2017, the disclosure of which is hereby incorporated by reference in its entirety. technical field [0003] The subject matter of the present disclosure relates to compositions and methods for inducing humoral and cellular immunity against tumors and cancer. In some embodiments, the presently disclosed subject matter involves administering to a subject in need thereof a therapeutic inducer of a humoral or cellular immune response to a gastrin peptide and / or an inducer of a cellular immune response against a tumor or cancer combined. Background technique [0004] Pancreatic cancer, commonly referred to as pancreatic ductal adenocarcinoma (PDAC), is a complex disease involving the continuous accumulation of genetic mutations in multiple cellular growth regulatory pathways. It begins as a relatively benign lesion i...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K39/395C07K14/00
CPCC07K7/06C07K7/08C07K14/00A61K39/0011C07K16/2818A61K2039/505A61K2039/6037A61K2039/627A61K2039/575A61P35/00A61K2039/852A61K39/001102A61K39/39541C07K2319/00A61K2300/00A61K39/385A61K2039/6081A61K39/39C07K16/2869
Inventor 林德·萨顿吉尔·P·史密斯尼古拉斯·奥斯本布赖恩·E·胡贝尔艾伦·卡托
Owner 癌症进展有限公司
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