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Major histocompatibility complex class ll-expressing cancer cell vaccine and methods of use for producing integrated immune responses

An immune response, cancer cell technology, applied in botanical equipment and methods, biochemical equipment and methods, cells modified by introducing foreign genetic material, etc., can solve the problem of not inducing TR-CD4 cells and so on

Pending Publication Date: 2021-06-08
HEALTH RES INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is currently no method to efficiently induce TR-CD4 cells in vivo
Accordingly, there is a continuing and unmet need for compositions and methods that improve the immune response to cancer and other immunogenic agents

Method used

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  • Major histocompatibility complex class ll-expressing cancer cell vaccine and methods of use for producing integrated immune responses
  • Major histocompatibility complex class ll-expressing cancer cell vaccine and methods of use for producing integrated immune responses
  • Major histocompatibility complex class ll-expressing cancer cell vaccine and methods of use for producing integrated immune responses

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Experimental program
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Effect test

Embodiment

[0043] Immunogenicity of engineered cancer cells was studied by introducing them into syngeneic C57BL / 6 mice.

[0044] In the EL4 lymphoma model, overexpression of CIITA alone did not alter tumor growth compared to parental EL4. In contrast, co-expression of CIITA and immunostimulatory molecules significantly delayed tumor growth. In particular, EL4 co-expressing OX40-L+CIITA or 4-1BB-L+CIITA were completely repelled. In this model, the three groups receiving EL4 overexpressing OX40-L+CIITA, 4-1BB-L+CIITA, and 4-1BB-L alone showed complete tumor elimination in all mice ( figure 2 ).

[0045] To assess the induction of long-term memory T cell responses by engineered cancer cells, mice rejecting EL4 overexpressing OX40-L+CIITA, 4-1BB-L+CIITA, or 4-1BB-L alone were rechallenged with parental EL4 ( image 3 A). Only a fraction of mice rejecting EL4 overexpressing 4-1BB-L alone or OX40-L+CIITA were resistant to rechallenge ( image 3 B). In contrast, all mice that rejected ...

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Abstract

Provided are modified cancer cells that are modified to co-express class II trans-activator (CIITA), and an immuno-stimulatory molecule. The immuno-stimulatory molecule is OX-40-ligand or 4-lBB-Ligand. Methods of making the cells are provided by introducing polynucleotides encoding the CIITA and the immune-stimulatory molecule into cancer cells. Methods of stimulating humoral and cell-mediated immune responses by administering the modified cancer cells, or polynucleotides encoding the CIITA and immune-stimulatory molecules are also provided. These approaches can be used to stimulate an immune response against any of a wide variety of cancer antigens.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 62 / 701,791, filed July 22, 2018, the disclosure of which is incorporated herein by reference. technical field [0003] The present disclosure relates generally to the prevention and treatment of cancer, and more particularly to compositions and methods for improving the immune response to cancer. Background technique [0004] Tumor antigen-specific CD4+ T cells, CD8+ T cells and B cells play a synergistic role in anti-tumor immunity. At the tumor site, CD8+ T cells (also known as cytotoxic T cells) are thought to be the main effector cells that destroy cancer cells. CD4+ T cells (also known as helper T cells) assist in the activation, function and maintenance of CD8+ T cells by activating antigen-presenting cells and / or secreting cytokines. CD4+ T cells also assist the activation of B cells to induce antibody secretion by expressing CD40-ligand (CD4...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/10C12N15/85C12N15/12A61K39/00A61P35/00
CPCC12N5/0693C12N2510/00C07K14/4702C07K14/70575C12N2740/16043C12N2840/203A61K48/005A61K39/0011A61K2039/5152A61P35/00A61K2039/575C12N15/85
Inventor 坤勒·奥顿斯塔克马萨·特苏基琼科·玛苏扎基
Owner HEALTH RES INC
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