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US-12616734-B2 - Chimeric antigen receptor specifically binding to cd 300C antigen or receptor thereof

US12616734B2US 12616734 B2US12616734 B2US 12616734B2US-12616734-B2

Abstract

A chimeric antigen receptor that specifically binds to a CD300c antigen or a receptor thereof, immune cells expressing the same, and uses thereof are disclosed. The chimeric antigen receptor that specifically binds to a CD300c antigen or a receptor thereof is able to specifically recognize cancer cells expressing the CD300c antigen or the CD300c receptor so that growth, metastasis, development, and the like of cancer can be suppressed in a direct and effective manner. Thus, it is expected that the chimeric antigen receptor can be effectively used as an immunotherapeutic agent for various cancers.

Inventors

  • Jaewon JEON
  • Sunwha Kim
  • Suin LEE

Assignees

  • CentricsBio, Inc.

Dates

Publication Date
20260505
Application Date
20220527
Priority Date
20191128

Claims (18)

  1. 1 . A chimeric antigen receptor comprising a binding domain specifically binding to a CD300c antigen or a receptor thereof, wherein the binding domain comprises: a heavy chain variable region comprising CDR1 to CDR3 comprising amino acid sequences represented by of Formulas (1) to (3), respectively, and a light chain variable region comprising CDR1 to CDR3 comprising amino acid sequences represented by Formulas (4) to (6), respectively: (1) (SEQ ID NO: 443) FTFSX1YX2MX3WVR, wherein X1=R, S, or D X2=A, G, or H X3=T, H, or S (2) (SEQ ID NO: 444) X1X2SX3X4GGX5TYYAX6, wherein X1=S, A, or T X2=M or I X3=G or S X4=T or S X5=T, S, or Y X6=D or E (3) (SEQ ID NO: 445) YCAX1X2X3X4X5X6X7X8X9X10X11W, wherein X1=R, V, or S X2=G or S X3=A, G, S, Y, or I X4=Y, A, Q, G, or R X5=G or L X6=F, R, I, M, or P X7=D, G, F, or L X8=H, F, D, or V X9=F, I, Y or not present X10=D or not present X11=Y or not present (4) (SEQ ID NO: 446) CX1X2X3X4X5X6X7X8X9X10X11X12X13W, wherein X1=R, S, or T X2=A, G, or R X3=S or N X4=Q, S, or N X5=S, I, or G X6=I, N, or G X7=G, I, T, or S X8=N, G, R, A, or K X9=Y, S, R, or G X10=N or not present X11=Y or not present X12=Lor V X13=N, Y, H, or Q (5) (SEQ ID NO: 447) X1X2X3X4X5X6X7GX8X9, wherein X1=D, E, S, or R X2=A, D, K, or N X3=S or N X4=N, K, or Q X5=L or R X6=E or P X7=T or S X8=I or V X9=P or R; and (6) (SEQ ID NO: 448) YCX1X2X3X4X5X6X7X8X9X10X11F, wherein X1=Q, S, or A X2=Q, S, or A X3=S, Y, or W X4=S, T, D, or A X5=A, S, D, or G X6=I, S, N, or T X7=P, S, L, N, or K X8=Y, T, S, N, or G X9=V, G, L or not present X10=P or not present X11=T, I, or V.
  2. 2 . The chimeric antigen receptor of claim 1 , further comprising a transmembrane domain and an intracellular signaling domain.
  3. 3 . The chimeric antigen receptor of claim 1 , wherein the binding domain comprises: (i) a heavy chain variable region, comprising: CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 19, SEQ ID NO: 31, SEQ ID NO: 43, SEQ ID NO: 55, SEQ ID NO: 67, SEQ ID NO: 79, SEQ ID NO: 91, SEQ ID NO: 103, SEQ ID NO: 115, SEQ ID NO: 127, SEQ ID NO: 139, SEQ ID NO: 151, SEQ ID NO: 163, SEQ ID NO: 175, SEQ ID NO: 187, SEQ ID NO: 199, SEQ ID NO: 211, SEQ ID NO: 223, SEQ ID NO: 235, SEQ ID NO: 247, SEQ ID NO: 259, SEQ ID NO: 271, SEQ ID NO: 283, and SEQ ID NO: 295; CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 8, SEQ ID NO: 20, SEQ ID NO: 32, SEQ ID NO: 44, SEQ ID NO: 56, SEQ ID NO: 68, SEQ ID NO: 80, SEQ ID NO: 92, SEQ ID NO: 104, SEQ ID NO: 116, SEQ ID NO: 128, SEQ ID NO: 140, SEQ ID NO: 152, SEQ ID NO: 164, SEQ ID NO: 176, SEQ ID NO: 188, SEQ ID NO: 200, SEQ ID NO: 212, SEQ ID NO: 224, SEQ ID NO: 236, SEQ ID NO: 248, SEQ ID NO: 260, SEQ ID NO: 272, SEQ ID NO: 284, and SEQ ID NO: 296; and CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 21, SEQ ID NO: 33, SEQ ID NO: 45, SEQ ID NO: 57, SEQ ID NO: 69, SEQ ID NO: 81, SEQ ID NO: 93, SEQ ID NO: 105, SEQ ID NO: 117, SEQ ID NO: 129, SEQ ID NO: 141, SEQ ID NO: 153, SEQ ID NO: 165, SEQ ID NO: 177, SEQ ID NO: 189, SEQ ID NO: 201, SEQ ID NO: 213, SEQ ID NO: 225, SEQ ID NO: 237, SEQ ID NO: 249, SEQ ID NO: 261, SEQ ID NO: 273, SEQ ID NO: 285, and SEQ ID NO: 297; and (ii) a light chain variable region, comprising: CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 10, SEQ ID NO: 22, SEQ ID NO: 34, SEQ ID NO: 46, SEQ ID NO: 58, SEQ ID NO: 70, SEQ ID NO: 82, SEQ ID NO: 94, SEQ ID NO: 106, SEQ ID NO: 118, SEQ ID NO: 130, SEQ ID NO: 142, SEQ ID NO: 154, SEQ ID NO: 166, SEQ ID NO: 178, SEQ ID NO: 190, SEQ ID NO: 202, SEQ ID NO: 214, SEQ ID NO: 226, SEQ ID NO: 238, SEQ ID NO: 250, SEQ ID NO: 262, SEQ ID NO: 274, SEQ ID NO: 286, and SEQ ID NO: 298; CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 11, SEQ ID NO: 23, SEQ ID NO: 35, SEQ ID NO: 47, SEQ ID NO: 59, SEQ ID NO: 71, SEQ ID NO: 83, SEQ ID NO: 95, SEQ ID NO: 107, SEQ ID NO: 119, SEQ ID NO: 131, SEQ ID NO: 143, SEQ ID NO: 155, SEQ ID NO: 167, SEQ ID NO: 179, SEQ ID NO: 191, SEQ ID NO: 203, SEQ ID NO: 215, SEQ ID NO: 227, SEQ ID NO: 239, SEQ ID NO: 251, SEQ ID NO: 263, SEQ ID NO: 275, SEQ ID NO: 287, and SEQ ID NO: 299; and CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 24, SEQ ID NO: 36, SEQ ID NO: 48, SEQ ID NO: 60, SEQ ID NO: 72, SEQ ID NO: 84, SEQ ID NO: 96, SEQ ID NO: 108, SEQ ID NO: 120, SEQ ID NO: 132, SEQ ID NO: 144, SEQ ID NO: 156, SEQ ID NO: 168, SEQ ID NO: 180, SEQ ID NO: 192, SEQ ID NO: 204, SEQ ID NO: 216, SEQ ID NO: 228, SEQ ID NO: 240, SEQ ID NO: 252, SEQ ID NO: 264, SEQ ID NO: 276, SEQ ID NO: 288, and SEQ ID NO: 300, or wherein the binding domain comprises the amino acid sequence represented by SEQ ID NO: 402.
  4. 4 . The chimeric antigen receptor of claim 3 , wherein (i) the heavy chain variable region comprises: CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 67, SEQ ID NO: 79, SEQ ID NO: 115, or SEQ ID NO: 211; CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 68, SEQ ID NO: 80, SEQ ID NO: 116, or SEQ ID NO: 212; and CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 69, SEQ ID NO: 81, SEQ ID NO: 117, or SEQ ID NO: 213, and (ii) the light chain variable region comprises: CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 10, SEQ ID NO: 70, SEQ ID NO: 82, SEQ ID NO: 118, or SEQ ID NO: 214; CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 71, SEQ ID NO: 83, SEQ ID NO: 119, or SEQ ID NO: 215; and CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 12, SEQ ID NO: 72, SEQ ID NO: 84, SEQ ID NO: 120, or SEQ ID NO: ID NO: 216.
  5. 5 . The chimeric antigen receptor of claim 1 , further comprising a signal peptide, a GS linker, a transmembrane domain, and an intracytoplasmic domain.
  6. 6 . The chimeric antigen receptor of claim 5 , wherein the signal peptide comprises a CD8a signal peptide.
  7. 7 . The chimeric antigen receptor of claim 5 , wherein the transmembrane domain comprises a CD8 hinge (hinge of cluster of differentiation 8) and a CD28 transmembrane domain.
  8. 8 . The chimeric antigen receptor of claim 5 , wherein the intracytoplasmic domain comprises a CD28 intracellular domain and a CD32 intracellular domain.
  9. 9 . A polynucleotide comprising a nucleic acid sequence encoding the chimeric antigen receptor of claim 1 .
  10. 10 . An expression vector comprising the polynucleotide of claim 9 .
  11. 11 . An immune cell comprising the chimeric antigen receptor of claim 1 , a polynucleotide encoding the chimeric antigen receptor, or an expression vector comprising the polynucleotide.
  12. 12 . The immune cell of claim 11 , wherein the immune cell includes any one or more selected from the group consisting of a monocyte, a macrophage, a T cell, a natural killer cell (NK cell), and a dendritic cell.
  13. 13 . A pharmaceutical composition for treatment of cancer expressing a CD300c antigen or a CD300c receptor, said pharmaceutical composition comprising the immune cell of claim 11 as an active ingredient.
  14. 14 . The pharmaceutical composition of claim 13 , wherein the cancer includes any one or more selected from the group consisting of colorectal cancer, rectal cancer, colon cancer, thyroid cancer, oral cancer, pharyngeal cancer, laryngeal cancer, cervical cancer, brain cancer, lung cancer, ovarian cancer, bladder cancer, kidney cancer, liver cancer, pancreatic cancer, prostate cancer, skin cancer, tongue cancer, breast cancer, uterine cancer, stomach cancer, bone cancer, and blood cancer.
  15. 15 . The pharmaceutical composition of claim 13 , further comprising another anticancer agent.
  16. 16 . The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition inhibits the proliferation, survival, metastasis, recurrence, or anticancer agent resistance of cancer.
  17. 17 . A method for treating cancer expressing a CD300c antigen or a CD300c receptor, the method comprising administering to a subject a composition comprising the immune cell of claim 11 as an active ingredient.
  18. 18 . The method of claim 17 , wherein the cancer includes any one or more selected from the group consisting of colorectal cancer, rectal cancer, colon cancer, thyroid cancer, oral cancer, pharyngeal cancer, laryngeal cancer, cervical cancer, brain cancer, lung cancer, ovarian cancer, bladder cancer, kidney cancer, liver cancer, pancreatic cancer, prostate cancer, skin cancer, tongue cancer, breast cancer, uterine cancer, stomach cancer, bone cancer, and blood cancer.

Description

CROSS REFERENCE This application is a bypass continuation-in-part application and claims benefits of PCT/KR2020/017230 filed Nov. 30, 2020, which claims priority based on Korean Patent Application Nos. 10-2019-0155027 filed Nov. 28, 2019 and 10-2020-0162200 filed on Nov. 27, 2020, and this application is a bypass continuation of PCT/KR2022/007384 filed May 24, 2022, which claims priority based on Korean Patent Application No. 10-2021-0066547 filed May 24, 2021, of which the contents are incorporated by reference in their entireties. SEQUENCE LISTING The content of the electronically submitted sequence listing, file name: Q276211_ST25; size: 220,190 bytes; and date of creation: May 16, 2022, filed herewith, is incorporated herein by reference in its entirety. TECHNICAL FIELD The present disclosure relates to a chimeric antigen receptor that specifically binds to a CD300c antigen or a receptor thereof, immune cells expressing the same, uses thereof, and the like. BACKGROUND ART Cancer is one of the diseases that account for the largest share of the causes of death in modern people. This disease is caused by changes in normal cells due to genetic mutations that result from various causes and refers to a malignant tumor that does not follow differentiation, proliferation, growth pattern, or the like of normal cells. Cancer is characterized by “uncontrolled cell growth.” This abnormal cell growth causes formation of a mass of cells called a tumor, which infiltrates the surrounding tissues and, in severe cases, may metastasize to other organs of the body. Cancer is an intractable chronic disease that is not fundamentally cured in many cases even if it is treated with surgery, radiotherapy, chemotherapy, and the like, causes pain to patients, and ultimately leads to death. In particular, in recent years, the global cancer incidence rate is increasing by 5% or higher every year due to increased elderly population, environmental deterioration, or the like. According to the WHO report, it is estimated that within the next 25 years the number of cancer patients will increase to 30 million, of which 20 million will die from cancer. Cancer drug treatments, that is, cancer chemotherapies are generally cytotoxic compounds, and treat cancer by attacking and killing cancer cells. However, these chemotherapies exhibit high adverse effects since they damage not only cancer cells but also normal cells. Thus, targeted cancer chemotherapies have been developed to decrease adverse effects. These targeted cancer chemotherapies were able to exhibit decreased adverse effects, but had a limitation in that resistance occurs with a high probability. Therefore, in recent years, interest in cancer immunotherapies, which use the body's immune system to decrease problems due to toxicity and resistance, is rapidly increasing. As an example of such cancer immunotherapies, immune checkpoint inhibitors have been developed which specifically bind to PD-L1 on the surface of cancer cells and inhibit its binding to PD-1 on T cells so that T cells are activated and attack cancer cells. However, even these immune checkpoint inhibitors are not effective in various types of cancer. Therefore, there is a need to develop novel cancer immune therapeutics that exhibit an equivalent therapeutic effect in various cancers. Meanwhile, chimeric antigen receptors (CARs) are artificial receptors designed to deliver antigen specificity to T cells, and comprise an antigen-specific domain that activates T cells and provides specific immunity, a transmembrane domain, an intracellular domain, and the like. Recently, studies are actively conducted on cancer immunotherapy using cells into which a gene encoding such a chimeric antigen receptor has been introduced, that is, a method for treating cancer through a therapy in which T cells are collected from a patient, a gene encoding a chimeric antigen receptor is introduced into these T cells and amplified, and transferred back into the patient. RELEVANT ART LITERATURE Patent Literature (Patent Literature 1) Korean Patent Laid-Open Publication No. 10-2016-0016725 A. DISCLOSURE Technical Problem An object of the present disclosure is to solve all of the above-mentioned problems. One object of the present disclosure is to provide a chimeric antigen receptor for preventing or treating cancer, comprising a binding domain that specifically binds to a CD300c antigen or a receptor thereof. Another object of the present disclosure is to provide an immune cell expressing the chimeric antigen receptor. Yet another object of the present disclosure is to provide an isolated nucleic acid molecule encoding the chimeric antigen receptor. Still yet another object of the present disclosure is to provide a vector comprising the nucleic acid molecule that encodes the chimeric antigen receptor. Still yet another object of the present disclosure is to provide an anticancer therapy using the chimeric antigen receptor or the immune cells compri