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Compositions and methods relating to macrophages and/or monocytes with adhered particles

A macrophage and monocyte technology, which can be used in drug combinations, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc. It can solve problems such as failure and loss of macrophages.

Pending Publication Date: 2021-01-08
PRESIDENT & FELLOWS OF HARVARD COLLEGE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, attempts at adoptive macrophage therapy have so far failed due to the propensity of macrophages to rapidly lose the desired phenotype

Method used

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  • Compositions and methods relating to macrophages and/or monocytes with adhered particles
  • Compositions and methods relating to macrophages and/or monocytes with adhered particles
  • Compositions and methods relating to macrophages and/or monocytes with adhered particles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0190] 1. An engineered cell composition comprising:

[0191] a. Monocytes or macrophages; and

[0192] b. A polymeric particle comprising an M1 polarizing cytokine polypeptide, wherein said particle is located on the cell surface of said monocyte or macrophage.

[0193] 2. The composition of paragraph 1, wherein the polymer particles are substantially disc-like in shape.

[0194] 3. The composition of paragraph 1, wherein the polymer particles are disc-like in shape.

[0195] 4. The composition of any of paragraphs 1-3, wherein the polymer particles have a size from about 3 μm x 150 nm to about 12 μm x 500 nm.

[0196] 5. The composition of any of paragraphs 1-4, wherein the polymer particles have a size of about 6 μm x 250 nm.

[0197] 6. The composition of any of paragraphs 1-5, wherein the polymer particles comprise:

[0198] a. A first region comprising one or more cell adhesion molecules (eg polyelectrolytes);

[0199] b. A second region comprising one or more struc...

Embodiment 1

[0396] Example 1: Cell backpack for adoptive macrophage therapy

[0397] Adoptive T-cell therapy has shown great promise in the treatment of many cancers, however, its efficacy depends on the knowledge and presence of relevant tumor-specific antigens. On the other hand, adoptive macrophage therapy allows its use in a wider range of tumors due to its intrinsic immune properties that elicit antigen-independent anticancer responses. Previous attempts to translate macrophage-mediated adoptive immunotherapy to the clinic have failed because therapeutic macrophages lose their antitumor M1 phenotype once exposed to the tumor microenvironment. Described herein are methods and compositions that overcome this obstacle by attaching IFN-γ-loaded antiphagocytic backpacks to the surface of macrophages. Knapsack provides a pool of IFN-γ to prevent phenotypic shift of macrophages from an anti-tumor phenotype, thus preserving their therapeutic activity. This approach provides a practical cli...

Embodiment 2

[0419] Four objectives to demonstrate the therapeutic efficacy of this approach are described here: (i) IFN-γ can be loaded into a backpack and its activity and release profile studied. Optimal loading and release rates can be determined; (ii) the effect of backpacks on monocytes can be studied in vitro. Factors such as the ability of the knapsack to maintain M1 polarization in response to tumor cell conditioned media can be tested by examining gene expression with RT-PCR. The viability of monocytes can be confirmed. Infiltration of tumor spheroids by knapsack-loaded monocytes can also be tested; (iii) in vivo biodistribution of knapsacks can be determined. Monocytes can be modified ex vivo using backpacks and administered to mice. Tumor accumulation and off-target distribution of backpacks can be measured. The toxicity of the knapsack itself can be assessed; (iv) the therapeutic efficacy of the monocyte-knapsack can be tested in vivo using relevant tumor models for which m...

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Abstract

Provided herein are polymeric particles and compositions (i.e., "backpacks") that can adhere to cells and provide delivery of payload immunomodulatory agents to those cells. For examples, the particles can adhere to macrophages and / or monocytes and release cytokines that promote an M1 or M2 phenotype to improve therapeutic efficacy of the cells.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62 / 616,519, filed January 12, 2018, and U.S. Provisional Application No. 62 / 634,267, filed February 23, 2018, by reference The contents of which are incorporated herein in its entirety. technical field [0003] The technology described herein relates to methods and compositions related to macrophages and / or monocytes having particles adhered to their cell surfaces. Background technique [0004] Adoptive T cell therapy has shown great therapeutic promise. Adoptive macrophage therapy has the potential to provide an equally effective treatment modality with even greater flexibility and wider applicability. However, attempts at adoptive macrophage therapy have so far failed due to the propensity of macrophages to rapidly lose the desired phenotype. Contents of the invention [0005] Described herein are ways that allow macr...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K35/15
CPCA61K38/19A61K38/191A61K38/193A61K38/20A61K38/204A61K38/208A61K38/217A61K45/06A61K9/5153A61K9/5138A61K9/5161A61K9/5169A61K31/728A61P17/02A61K39/4614A61K2239/49A61K39/4622A61K39/4644A61K2300/00A61K47/6901A61P35/00A61K35/15A61K38/2026
Inventor 萨米尔·米特拉戈特里迈克尔·安德鲁·埃文斯查尔斯·怀亚特·谢尔兹四世
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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