Compositions and methods for adoptive cell therapy for cancer

{
  "publication_number": "US2026103696A1",
  "country": "US",
  "kind": "A1",
  "title": "Compositions and methods for adoptive cell therapy for cancer",
  "abstract": "Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.",
  "claims": [
    "1. A method for preparing immune cells for cancer therapy, comprising isolating immune cells from a donor subject, transducing the immune cells with (a) a nucleic acid that encodes a first prodrug converting enzyme, wherein the first prodrug converting enzyme is expressed in the cytoplasm of the immune cell; and optionally, (b) a nucleic acid that encodes (i) a second prodrug converting enzyme, wherein the second prodrug converting enzyme is expressed on the surface of the immune cell or is secreted and/or (ii) a nucleic acid that encodes a receptor that binds to a target antigen and/or a nucleic acid encoding the receptor. 2. A compound of Formula I or a zwitterion, pharmaceutically acceptable salt, and/or solvate thereof, wherein X is O or NH; X 2 is N or C H; X 3 is OH or H; W 1 is H or NH - R 3; two of R 1, R 2, and R 3 are H and the remaining R 1, R 2, and R 3 is X 4 and X 5 are each independently O or NH; X 6 is O, NH, CH 2, or C(Me) 2; R 4, R 5, R 6, R 7, and R 8 are each independently H, - (CH 2) 3 - NH(NH) - NH 2, - (CH 2) 3 - NH 2, - (CH 2) 4 - NH 2, - CH 2 - C(O)OR 13a, - (CH 2) 2 - C(O)OR 13b, and R 9, R 10, R 11, R 12, R 13, R 13a, and R 13b are each independently alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, - CH 2 - OC(O)-alkyl, - CH 2 - OC(O)-aryl, - CH 2 - OC(O)-heteroaryl, - CH 2 - OC(O)-aralkyl, or - CH 2 - OC(O)-heteroaralkyl. 3. A compound of Formula II or a zwitterion, pharmaceutically acceptable salt, and/or solvate thereof, wherein X 7 and X 8 are each independently Cl, Br, I, O - S(O) 2 CH 3, or O - S(O) 2 -tolyl; X 9 is - C(O) - O, - C(O) - NH, O, or NH; R 14 is a bond, alkylene, arylene, aralkylene, heteroarylene, or heteroaralkylene; R 15 is X 10 and X 11 are each independently O or NH; X 6 is O, NH, CH 2, or C(Me) 2; X 12 is O, NH, CH 2, or C(Me) 2; R 16, R 17, R 18, R 19, and R 20 are each independently H, - (CH 2) 3 - NH(NH) - NH 2, - (CH 2) 3 - NH 2, - (CH 2) 4 - NH 2, - CH 2 - C(O)OR 25a, - (CH 2) 2 - C(O)OR 25b, and R 21, R 22, R 23, R 24, R 25, R 25a, and R 25b are each independently alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, - CH 2 - OC(O)-alkyl, - CH 2 - OC(O)-aryl, - CH 2 - OC(O)-heteroaryl, - CH 2 - OC(O)-aralkyl, or - CH 2 - OC(O)-heteroaralkyl, provided that R 21, R 22, R 23, R 24, R 25, R 25a, and R 25B are each independently not tert-butyl. 4. A compounds of Formula III or a zwitterion, pharmaceutically acceptable salt, and/or solvate thereof, wherein R 55 is X 35 and X 36 are each independently O or NH; X 37 is O, NH, CH 2, or C(Me) 2; R 56, R 57, R 58, R 59, and R 60 are each independently H, - (CH 2) 3 - NH(NH) - NH 2, - (CH 2) 3 - NH 2, - (CH 2) 4 - NH 2, - CH 2 - C(O)OR 6 a, (CH 2) 2 - C(O)OR 65, and R 61, R 62, R 63, R 64, R 65, R 65a, and R 65b are each independently alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, - CH 2 - OC(O)-alkyl, - CH 2 - OC(O)-aryl, - CH 2 - OC(O)-heteroaryl, - CH 2 - OC(O)-aralkyl, or - CH 2 - OC(O)-heteroaralkyl. 5. A compound that is or a zwitterion, pharmaceutically acceptable salt, and/or solvate thereof."
  ],
  "description_excerpt": "Adoptive and engineered T cell therapies, including chimeric antigen receptor (CAR) T cells, T cell receptor (TCR) engineered T cells, and antigen adopted T cells, have emerged recently as important therapies for cancer. First generation CARs were designed by fusing the scFv to the intracellular signaling domain of the CD3-ζ chain, whereas second generation CARs added CD28-CD80 costimulation in which the CD28 signaling domain was incorporated into the CAR construct (i.e.: “28ζ CAR”) for improved T cell activation and efficacy. However, greater potency and mechanisms to defeat the immunosuppressive tumor microenvironment are still needed for many cancer types. Resistance to the activity of these cells, relapse, and toxicity are still important hurdles to their success. Recent reports of significant toxicities and even deaths after CAR T cell therapy, and TCR T cell therapy, and the continuing incidence of GVHD with its associated short- and long-term morbidity and mortality, call for new methods to potentiate efficacy, and at the same time, to better control the various adoptive cell therapies.\n\nProvided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a receptor that binds to a target antigen and a first prodrug converting enzyme, wherein the first prodrug converting enzyme is expressed in the cytoplasm (e.g., intracellularly) of the engineered immune cells to allow selective destruction of the cells.",
  "cpc": [
    "C12N 9/485",
    "A61K 2239/48",
    "A61K 2239/49",
    "A61K 2239/50",
    "A61K 2239/55",
    "A61K 2239/59",
    "A61K 38/00",
    "A61K 40/11",
    "A61K 40/31",
    "A61K 40/4211",
    "A61K 40/4243",
    "A61K 40/4244",
    "A61K 40/427",
    "A61K 45/06",
    "A61K 9/0019",
    "A61P 35/00",
    "C07D 239/94",
    "C07D 501/16",
    "C07D 519/00",
    "C07K 14/52",
    "C07K 16/2803",
    "C07K 2317/24",
    "C07K 2317/622",
    "C07K 2319/03",
    "C07K 2319/30",
    "C07K 2319/35",
    "C12N 5/0636",
    "C12Y 304/17011"
  ],
  "ipc": [
    "A61K 38/00",
    "A61K 40/11",
    "A61K 40/31",
    "A61K 40/42",
    "A61K 45/06",
    "A61K 9/00",
    "A61P 35/00",
    "C07D 239/94",
    "C07D 501/16",
    "C07D 519/00",
    "C07K 14/52",
    "C07K 16/28",
    "C12N 5/0783",
    "C12N 9/48"
  ],
  "assignees": [
    "Memorial Sloan Kettering Cancer Center"
  ],
  "inventors": [
    "David A. Scheinberg",
    "Thomas J. Gardner",
    "Derek S. Tan",
    "Jonghan LEE",
    "Ivo Lorenz"
  ],
  "filing_date": "2025-03-03",
  "publication_date": "2026-04-16",
  "priority_date": "2017-06-30",
  "application_number": "US-202519069114-A",
  "family_id": "64742742",
  "cited_by_count": 0
}