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Chimeric antigen receptor tumor infiltrating lymphocytes

A lymphocyte and tumor infiltration technology, applied in the direction of anti-tumor drugs, animal cells, antibody medical components, etc., can solve the problem that PBL cannot penetrate solid tumor blocks, etc.

Pending Publication Date: 2021-04-09
H 李 莫菲特癌症中心和研究所公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, activated PBLs are biologically unable to penetrate solid tumor masses

Method used

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  • Chimeric antigen receptor tumor infiltrating lymphocytes
  • Chimeric antigen receptor tumor infiltrating lymphocytes
  • Chimeric antigen receptor tumor infiltrating lymphocytes

Examples

Experimental program
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Effect test

Embodiment 1

[0132] Figure 1A Cr for TILs against MC-38 is shown 51 Release assay. Figure 1B MC-38 tumor volumes in mice receiving TIL are shown. Figure 1C It was shown that TILs tracked by CD45.2 staining are preferentially retrafficked back to MC-38 tumors.

Embodiment 2

[0134] MC38 tumors were generated in donor mice (CD45.2+) by subcutaneous injection of tumor cell suspension. Once tumors were formed, CD45.2+ TILs were isolated and expanded ex vivo in the presence of IL-2. These were injected into tumor bearing recipient mice (CD45.1+). The tissue distribution of adoptively transferred TILs was tracked by flow cytometry due to the expression of CD45.2.

[0135] Using this method, adoptively transferred TILs (CD3+CD45.2+) were observed to be gradually enriched in tumors over the course of one week ( figure 2 ). The majority of metastatic TILs relocalized to recipient mouse tumors were CD8+ T cells ( figure 2 ).

[0136] Although a small fraction of adoptively transferred TILs was transiently detected in the spleen, lymph nodes, and bone marrow of recipient mice on day 1; by day 7 post-infusion, nearly all transferred TILs (and all CD8+ transferred TILs) are transported to the tumor ( image 3 ). The results indicated that TI...

Embodiment 3

[0141] Tumor infiltrating lymphocytes from melanoma patients were expanded in the presence of IL-2 following standard procedures. Forty-eight hours after REP, cells were transduced with a retroviral vector encoding an anti-IL13RA2 CAR (Hu07-28z). Transduction was repeated one day later, and CAR expression was assessed by flow cytometry after staining with biotinylated protein-L and PE-conjugated streptavidin ( Figure 5 ).

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Abstract

Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, tumor infiltrating lymphocytes (TILs) are genetically engineered to express chimeric antigen receptor (CAR) polypeptides to produce CAR-TILs that can be used with adoptive cell transfer to target, penetrate, and kill solid tumor masses. Therefore, also disclosed are methods of providing an immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed CAR-TILs.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 62 / 683,792, filed June 12, 2018, and Application Serial No. 62 / 857,054, filed June 4, 2019, the entire contents of which are incorporated herein by reference. Background technique [0003] Surgery, radiation therapy and chemotherapy have been standard accepted methods of treating cancer including leukemia, solid tumors and metastasis. Immunotherapy (sometimes called biological therapy (biotherapy) or biological response modifier therapy), which directly or indirectly uses the body's immune system to shrink or eradicate cancer, has been studied over the years as an adjunct to conventional cancer therapy. It is believed that the human immune system is an untapped resource for cancer therapy and that once components of the immune system are properly utilized, effective treatments can be developed. [0004] Chimeric antigen receptors (CARs) are engineered ...

Claims

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Application Information

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IPC IPC(8): A61K48/00C12N5/071A61K39/00C12N15/00C07K16/00C07H21/04
CPCA61K48/00C12N5/0636C07K14/7051C07K2319/03C07K2319/33C07K2319/70A61K2039/82A61P35/00C12N2510/00C12N2740/10043A61K2239/57A61K39/4631A61K39/4611A61K39/464419A61K39/4644A61K35/17A61K39/39541C07K14/70589C07K16/2818C07K16/2827C07K16/2866C07K2319/02
Inventor 詹姆斯·穆勒丹尼尔·阿贝特-达加
Owner H 李 莫菲特癌症中心和研究所公司
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