IP Library › Granted Patent US 12,398,192
Granted Patent B2
US 12,398,192 · App. 17/250,832 · Granted Aug 26, 2025

Cancer treatment with 237 CAR-T cell based therapeutics recognizing the Tn epitope

Inventors: Hans Schreiber (Chicago, IL); David Kranz (Champaign, IL); Karin Schreiber (Chicago, IL); Yanran He (Chicago, IL); Preeti Sharma (Urbana, IL)
Assignees: The University of Chicago; The Board of Trustees of the University of Illinois
C07K14/7051A61K40/11A61K40/31A61K40/4259A61P35/00C07K14/70535C07K16/18C12N5/0638A61K2239/13A61K2239/31A61K2239/38A61K2239/48A61K2239/59
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Quick Facts
Patent No.
US 12,398,192
App. No.
17/250,832
Granted
Aug 26, 2025
Kind
B2
Abstract

The disclosure provides Tn epitope-specific chimeric antigen receptors and scFvs, including soluble scFvs and multimeric scFvs, as well as methods of identifying cancer subjects and cancer subject sub-populations amenable to anti-Tn immunotherapy and methods of treating cancer.

Claims (19)

1. A chimeric antigen receptor (CAR) that specifically binds a Tn glycopeptide comprising:

(a) a single chain variable fragment (scFv) that specifically binds a Tn glycopeptide, wherein the scFv comprises a heavy chain complementarity determining region 1 (CDRH1), a CDRH2, a CDRH3, a light chain complementarity determining region 1 (CDRL1), and a CDRL2 of SEQ ID NO: 19, and a CDRL3 comprising a variant sequence of TTWAP, STWAP, STWSP, STWGP, STWQP, STWEP, SVWEP, STWVP, STHQP, SLGQP, or TNGKP at positions 96-100 of SEQ ID NO: 19; and

(b) a T-cell signaling domain.

2. The chimeric antigen receptor of claim 1 , wherein the scFv is a variant of the wild-type scFv of antibody 237 comprising at least one amino acid variation from the wild-type antibody 237 light chain complementarity determining region 3 sequence at positions 96-100 of SEQ ID NO:19.

3. The chimeric antigen receptor of claim 1 , wherein the CAR comprises an antibody 237 light chain complementarity determining region 3 sequence comprising the amino acids of positions 96-100 of SEQ ID NO:27.

4. The chimeric antigen receptor of claim 1 , wherein the CAR comprises an antibody 237 light chain complementarity determining region 3 sequence comprising the amino acids of positions 96-100 of SEQ ID NO:28.

5. The chimeric antigen receptor of claim 1 , wherein the CAR comprises an antibody 237 light chain complementarity determining region 3 sequence comprising the amino acids of positions 96-100 of SEQ ID NO:20.

6. The chimeric antigen receptor of claim 1 , wherein the T-cell signaling domain is CD3ζ or FcRγ.

7. The chimeric antigen receptor of claim 6 , wherein the FcRγ is FcεRγ.

8. The chimeric antigen receptor of claim 7 , further comprising a CD28 transmembrane region, an ICOS transmembrane region, 4-1BB, or OX-40.

9. The chimeric antigen receptor of claim 1 , wherein the chimeric antigen receptor comprises the CD28 transmembrane region, and further comprises 4-1BB, OX-40, or Lck.

10. The chimeric antigen receptor of claim 1 wherein the CAR comprises the sequence set forth in SEQ ID NOs: 21, 22, 23 or 24.

11. A soluble cancer-specific 237 single chain variable fragment (scFv) variant that specifically binds a Tn glycopeptide comprising a heavy chain complementarity determining region 1 (CDRH1), a CDRH2, a CDRH3, a light chain complementarity determining region 1 (CDRL1), and a CDRL2 of SEQ ID NO:19, and a variant of a CDRL3 comprising a variant sequence of TTWAP, STWAP, STWSP, STWGP, STWQP, STWEP, SVWEP, STWVP, STHOP, SLGQP, or TNGKP at positions 96-100 of SEQ ID NO: 19.

12. The 237 scFv variant of claim 11 , wherein the scFv is a variant of the wild-type scFv of antibody 237 comprising the heavy chain variable region amino acid sequence at positions 127-244 of SEQ ID NO:19 and a variant of the light chain variable region amino acid sequence at positions 1-111 of SEQ ID NO:19, wherein the variant comprises at least one amino acid variation from the wild-type antibody 237 light chain complementarity determining region 3 sequence at positions 96-100 of SEQ ID NO: 19.

13. The 237 scFv variant of claim 11 , wherein a nanomolar concentration of the 237 scFv variant detectably binds a Tn epitope or exhibits detectable binding to a target Tn epitope that is not detectably bound by the wild-type 237 scFv at a nanomolar concentration.

14. The 237 scFv variant of claim 11 , wherein the scFv is a multimer.

15. The 237 scFv variant of claim 14 , wherein the multimer is a tetramer.

16. A cell expressing a detection agent, wherein the detection agent is the soluble scFv variant of claim 13 and wherein a nanomolar or sub-nanomolar concentration of the detection agent detectably binds to a Tn-glycopeptide with truncated glycosylation.

17. An engineered T-cell comprising the CAR of claim 1 .

Assignments (3)
CONFIRMATORY LICENSE Recorded Nov 14, 2023
From: UNIVERSITY OF CHICAGO
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065566/0091 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 11, 2022
From: SCHREIBER, HANS; SCHREIBER, KARIN; HE, YANRAN
To: THE UNIVERSITY OF CHICAGO
Reel/Frame 059563/0945 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 11, 2022
From: KRANZ, DAVID; SHARMA, PREETI
To: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS
Reel/Frame 059564/0005 →
Continuity (2)
Provisional Application 62729951 · Sep 11, 2018
Related Publication 20220047631A1 · Feb 17, 2022
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