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Immunogenic composition for the treatment of cancer

A composition, cancer technology, applied in the field of immunotherapy, which can solve problems such as no success

Pending Publication Date: 2020-05-19
J 梅利埃夫 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The use of autologous tumor cells as a potential tool in immunotherapy has been described previously, but so far such attempts have had little success due to the inability of tumor cells to induce sufficient T cell responses

Method used

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  • Immunogenic composition for the treatment of cancer
  • Immunogenic composition for the treatment of cancer
  • Immunogenic composition for the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0170] Example 1: Materials and methods

[0171] Cell Lines and Culture

[0172] Early passage melanoma cell lines ANRU, ROAL and KADA were established from patients at the Oncology Clinic of Karolinska University Hospital (Ethical Permission: #2011 / 143-32 / 1) according to published protocols. The 21 mycoplasma-free (MycoAlert kit) cell lines were at their 15th to 45th passages when used in this study.

[0173] Culture and Expansion of Tumor-Infiltrating Lymphocytes

[0174] Culturing and expansion of tumor infiltrating lymphocytes was performed as previously published. 4 A tumor (about 0.5 cm3) was cut into 1 mm3 pieces. Place each piece in one well of a 24-well plate containing 1 mL / well of CellGro medium supplemented with 2% autologous plasma (produced by centrifugation and heat inactivation of plasma collected on the day of surgery) and 6,000 IU / mL IL-2 (Proleukin, Novartis, Basel, Switzerland). On day 1 of culture, half the medium volume in each well was replaced wi...

Embodiment 2

[0177] Example 2: JQ1 is differentially sensitive to melanoma cells recognized by autologous TILs.

[0178] Here we show that treatment of patient-derived early-passage melanoma cell lines with JQ1 enhances recognition of autologous TILs. To investigate the potential inhibitory effect of BET inhibition on constitutive and induced PD-L1 expression, we also investigated the sensitization effect of JQ1 binding to IFNγ. Furthermore, treatment of cells by IFNγ alone provided insight into the magnitude of the potential sensitization of JQ1 compared to known physiological cues for target cell sensitization for T cell recognition. Meanwhile, PD-L1 and HLA class I expression in pretreated tumor cells were assessed by flow cytometry to find out whether functional observations in tumor-TIL co-cultures were related to changes in PD-L1 expression or HLA class I expression Related, both markers are key determinants of T cell activation upon recognition of target cells.

[0179] After cu...

Embodiment 3

[0183] Example 3: JQ1 enhances tumor recognition by TIL independently of PD-L1.

[0184] Next, we set out to further demonstrate that JQ1 can enhance TIL recognition of functional tumors regardless of the effect on PD-L1. To test this, we co-cultured ANRU tumor cells with autologous TILs for 24 h in the presence and absence of a PD-L1 blocking antibody. Suitable PD-L1 blocking antibodies are commercially available, including anti-human CD274 (B7-H1, PD-L1) antibody (clone 29E.2A3; catalog number 329709; Biolegend), anti-human CD274 (B7-H1, PD -L1) antibody (clone MIH3; Cat. No. 374502; Biolegend), anti-PD-L1 (CD274) neutralizing antibody (Cat. No. 71213; BPS Bioscience), PD-L1 / B7-H1 / CD274 blocking antibody (clone R639; catalog No. 10084-R639; SinoBiological) and human PD-L1 / B7-H1 antibody (Cat. No. AF156; R and D Systems). Tumor cells were pretreated for 12, 24, 48, and 72 h to examine any PD-L1 induction or inhibition over time by flow cytometry, and to define the tempora...

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Abstract

The invention relates to the field of immunotherapy, more in particular to a composition for use in the treatment of cancer. The invention also relates to a composition obtainable by such a method, such as a pharmaceutical composition. More in particular, the invention relates to an ex vivo method for obtaining a composition suitable for the treatment of cancer in a subject, comprising the steps of providing primary tumor cells derived from the subject, and ex vivo contacting the tumor cells with an inhibitor of a bromodomain and extra-terminal domain family member (BET inhibitor).

Description

technical field [0001] The present invention relates to the field of immunotherapy, and more particularly, to compositions useful in the treatment of cancer. The invention also relates to compositions, such as pharmaceutical compositions, obtainable by this method. Background technique [0002] In recent years, immunotherapeutic approaches for cancer have seen a massive increase, with remarkable clinical success achieved through the use of antibodies that block immune checkpoint molecules. 1 Encouraging results have also been obtained in cancer patients receiving other types of immunotherapy, such as adoptive transfer of ex vivo activated T cells and various therapeutic vaccination strategies. 2-7 [0003] Despite these significant advances, many immunotherapies have failed to induce clinical benefit in large numbers of cancer patients. The main reason for this is that the immune evasion mechanisms employed by tumors often render anti-tumor immunity ineffective. In this ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00
CPCA61K39/0011A61K2039/5152A61K2039/55522A61K9/0019A61K39/001102A61K39/00119A61K45/00C07K14/4703
Inventor J·梅利埃夫R·V·R·基斯林
Owner J 梅利埃夫
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