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Cancer vaccine composition and method for preventing and/or treating cancer by using same

A cancer vaccine, cancer cell technology, applied in breast cancer vaccines, vaccines, cancer antigen components, etc.

Pending Publication Date: 2022-03-18
DANA FARBER CANCER INST INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Although TGFβ signaling can act as a tumor suppressor and tumor promoter, the ability to harness TGFβ signaling for desired therapeutic purposes remains a matter of debate

Method used

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  • Cancer vaccine composition and method for preventing and/or treating cancer by using same
  • Cancer vaccine composition and method for preventing and/or treating cancer by using same
  • Cancer vaccine composition and method for preventing and/or treating cancer by using same

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0975] Example 1: Materials and methods for Examples 2-7

[0976] a.Cell culture

[0977] After adding 10% fetal bovine serum (FBS), 25ng / ml hydrocortisone, 5μg / ml insulin, 8.5ng / ml cholera toxin, 0.125ng / ml epidermal growth factor (EGF), 5μM Y-27632Rock1 inhibitor, penicillin PP and PP T breast cancer cells. for PP T cells, new 4ng / ml TGFβ1 was added to the medium every three days. at 37°C in 5% CO 2 Cells were grown in a humid environment. NMuMG, HMEC, MCF10A, ZR-75-1, MDA-MB-453, MDA-MB-231, MCF7, BT549, HCC1954, and HCC70 cells were purchased from the American Type Culture Collection (ATCC) and cultured according to the manufacturer's instructions .

[0978] b. Antibodies and reagents

[0979] TGFβ1 (#GF111) was purchased from Millipore (Billerica, MA, USA). FITC anti-mouse CD45(30-F11), PE / Dazzle were purchased from Biolegend (San Diego, CA, USA) TM 594 anti-mouse CD3(145-2C11), APC / Cy7 anti-mouse CD4(RM4-5), Alexa 700 anti-mouse CD8 (53-6.7), APC anti-mouse ...

example 2

[1002] Example 2: TGFβ-treated tumor cells induce T cell-dependent anti-tumor immune responses.

[1003] Transforming growth factor beta (TGFβ) is a pluripotent cytokine that plays a key role in regulating embryonic development, cell metabolism, tumor progression, and immune system homeostasis (David and Massague (2018), Nature Reviews Molecular Cell Biology, 19:419-435). After TGFβ binds to its receptor on the plasma membrane, it regulates the expression of its downstream genes in a Smad-dependent and independent manner ( Figure 16 ).

[1004] Loss of the tumor suppressors p53 or PTEN is the most common event in human cancers (Lawrence et al. (2014) Nature 505:495-501). Most advanced epithelial tumors, including triple-negative breast cancer (TNBC), lack p53 and PTEN (The Cancer Genome Atlas Network (2012), Nature, 490:61-70). A syngeneic genetically engineered mouse model (GEMM) of TNBC derived from female FVB mice (carrying K14-Cre; Trp53 L / L ; Pten L / L Concurrent abl...

example 3

[1006] Example 3: DCs play an important role in mediating TGFβ-induced anti-tumor immune responses.

[1007]Meanwhile, 6 days after transplantation, PP isolated from recipient mice and PP T Transcriptome analysis of a panel of 4604 cancer and immune-related genes on tumor tissue. Obviously, compared with PP tumors, PP T Expression of genes with Gene Ontology (GO) terms associated with activation of multiple immune pathways was significantly upregulated in tumors ( Figure 4A ). Genes encoding cytokines, cytokine receptors, and T cell co-stimulatory molecules were further confirmed to be significantly upregulated by real-time quantitative PCR ( Figure 4B ). Furthermore, compared with PP tumors, PP T Genes encoding class I and class II major histocompatibility complex (MHC) components, such as H2-D1, H2-Ab1, and Cd74, were significantly upregulated in tumor sites ( Figure 4B ). These data further confirm that PP T Cells are able to elicit robust immune responses in the...

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Abstract

The present invention is based, in part, on cancer vaccine compositions comprising PTEN and p53-deficient cancer cells comprising an activated TGF [beta]-Smad / p63 signaling pathway and methods of their use in the prevention and / or treatment of cancer.

Description

[0001] Cross references to related patent applications [0002] This application claims the benefit of priority to U.S. Provisional Application No. 62 / 876,416, filed July 19, 2019; the entire contents of said application are hereby incorporated by reference in their entirety. [0003] Statement of Rights [0004] This invention was made with government support under grant numbers P50CA168504, CA233810, CA187918, and R35 CA210057 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0005] Transforming growth factor beta (TGFβ) is a pluripotent cytokine that plays a key role in regulating embryonic development, cell metabolism, tumor progression, and immune system homeostasis (David and Massague (2018), Nature Reviews Molecular Cell Biology, 19:419-435). After TGFβ binds to receptors on the cell membrane, it regulates the expression of its downstream genes either dependent on Smad or independent of Smad. TG...

Claims

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Application Information

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IPC IPC(8): A61K39/39C12N5/09C12N5/16A61K38/54
CPCA61K39/0011A61K45/06A61K35/13A61K38/1841A61K2039/5152A61P35/00A61K39/001134A61K2039/5156A61K2300/00A61K2039/812A61K2039/575
Inventor J·赵Y·唐X·程
Owner DANA FARBER CANCER INST INC