JP-2025515473-A5 -

Dates

Publication Date

20260508

Application Date

20230425

Description

Summary This disclosure includes a disclosure of modified cytotoxic T cells (mCTLs), and mCTLs are, a) one or more nucleic acids comprising a nucleotide sequence encoding a T cell receptor (TCR) specific to an MHC class I polypeptide that presents a human papillomavirus (HPV) E7 peptide, including the amino acid sequence YMLDLQPETT (SEQ ID NO: 1 ) ("HPV E7 11-20 TCR") or YMLDLQPET (SEQ ID NO: 2) ("HPV E7 11-19 TCR") (collectively referred to as "HPV E7 11-19/20 TCR"), and b) one or more nucleic acids comprising a nucleotide sequence encoding another polypeptide, such as an antigen-binding polypeptide, which includes an antigen-binding domain specific to a CAR or cancer-associated antigen. The disclosure also includes a method for generating mCTLs. The disclosure also provides a method for treating cancer, which includes administering mCTLs to an individual in need. This disclosure also includes disclosures of mCTLs having TCRs other than HPV E7 11-19/20 TCRs, and disclosures of modified T cells other than NK cells, such as modified cells, that are modified to present both TCRs and CARs or other cancer-related antigen-binding domains. [Invention 1001] A certain amount of modified cytotoxic T cells ("mCTLs"), a) One or more nucleic acids comprising a nucleotide sequence encoding a T cell receptor (TCR) specific to an MHC class I polypeptide that presents the human papillomavirus (HPV) E7 peptide containing the amino acid sequence YMLDLQPETT (SEQ ID NO: 1) or YMLDLQPET (SEQ ID NO: 2), b) One or more nucleic acids containing a nucleotide sequence encoding a chimeric antigen receptor (CAR) Includes, The CAR comprises an antigen-binding domain specific to cancer-associated antigens, and the proportion of target mCTL cells in the composition exceeds at least 1% of the total number of T cells in the composition. The aforementioned amount of mCTL. [Invention 1002] A certain amount of modified cytotoxic T cells ("mCTLs"), a) A T cell receptor (TCR) specific to an MHC class I polypeptide that presents the human papillomavirus (HPV) E7 peptide containing the amino acid sequence YMLDLQPETT (SEQ ID NO: 1) or YMLDLQPET (SEQ ID NO: 2), b) Chimeric antigen receptor (CAR) and Includes, The CAR comprises an antigen-binding domain specific to cancer-associated antigens, and the proportion of target mCTL cells in the composition exceeds at least 1% of the total number of T cells in the composition. The aforementioned amount of mCTL. [Invention 1003] A certain amount of modified cytotoxic T cells ("mCTLs"), a) A heterologous T cell receptor (TCR) specific to an MHC class I polypeptide that presents the human papillomavirus (HPV) E7 peptide containing the amino acid sequence YMLDLQPETT (SEQ ID NO: 1) or YMLDLQPET (SEQ ID NO: 2), b) Chimeric antigen receptor (CAR) and Includes, The CAR includes an antigen-binding domain specific to cancer-related antigens. The aforementioned amount of mCTL. [Invention 1004] The aforementioned CAR, a) Extracellular domain including the antigen-binding domain, b) Transmembrane region, and c) Cytoplasmic domains containing intracellular signaling domains A certain amount of mCTL, including any of the inventions 1001 to 1003. [Invention 1005] A certain amount of mCTLs of the present invention 1004, wherein the cytoplasmic domain contains one or more costimulatory polypeptides. [Invention 1006] A certain amount of mCTL of the present invention 1005, wherein the aforementioned co-stimulatory polypeptide is selected from CD28, 4-1BB, and OX-40. [Invention 1007] A composition according to any one of the present invention 1004 to 1006, wherein the intracellular signaling domain includes a signaling domain from the zeta chain of human CD3. [Invention 1008] An amount of mCTL according to any of the present inventions 1001 to 1007, wherein the antigen-binding domain is a single-stranded Fv polypeptide or a nanobody. [Invention 1009] The CAR is a single polypeptide chain CAR, in any amount of mCTL as described in invention 1001 to 1008. [Invention 1010] The CAR comprises at least two polypeptide chains in any amount of mCTL according to any of the inventions 1001 to 1008. [Invention 1011] Any amount of mCTLs from any of the inventions 1001 to 1010, wherein the cancer-related antigen is selected from AFP, BCMA, CD10, CD117, CD123, CD133, CD128, CD171, CD19, CD20, CD22, CD30, CD33, CD34, CD38, CD5, CD56, CD7, CD70, CD80, CD86, CEA, CLD18, CLL-1, cMet, EGFR, EGFRvIII, EpCAM, EphA2, GD-2, Glypican-3, GPC3, HER-2, Kappa immunoglobulin, LeY, LMP1, Mesothelin, MG7, MUC1, NKG2D ligand, PD-L1, PSCA, PSMA, ROR1, ROR1R, TACI, and VEGFR2. [Invention 1012] The aforementioned TCR, (i) An α-chain having at least 90% amino acid sequence identity with the α-chain amino acid sequence shown in Figure 2A, (ii) Having at least 90% amino acid sequence identity with the β-chain amino acid sequence shown in Figure 2B A certain amount of mCTL, including any of the inventions 1001 to 1011. [Invention 1013] The aforementioned TCR, (i) A