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Description
[本発明1001]
単離された修飾ヒトキヌレニナーゼ酵素であって、配列番号：1のヒトキヌレニナーゼ酵素に少なくとも90％同一であるアミノ酸配列を有し、かつＬ8Ｐ、Ｋ38Ｅ、Ｙ47Ｌ、Ｉ48Ｆ、Ｋ50Ｑ、Ｉ51Ｍ、Ｓ60Ｎ、Ｋ64Ｎ、Ｄ65Ｇ、Ｅ66Ｋ、Ｎ67Ｄ、Ｎ67Ｐ、Ｄ67Ｓ、Ａ68Ｆ、Ａ68Ｔ、Ａ68Ｖ、Ｆ71Ｌ、Ｆ71Ｍ、Ｌ72Ｎ、Ｋ84Ｅ、Ｅ88Ｎ、Ｅ89Ｋ、Ｅ89Ｓ、Ｅ90Ｑ、Ｄ92Ｅ、Ｋ93Ｎ、Ｋ93Ｔ、Ａ95Ｈ、Ａ95Ｑ、Ｋ96Ｎ、Ｉ97Ｈ、Ｉ97Ｌ、Ｉ97Ｖ、Ａ98Ｇ、Ａ99Ｇ、Ａ99Ｉ、Ａ99Ｒ、Ａ99Ｓ、Ａ99Ｔ、Ａ99Ｖ、Ｙ100Ｎ、Ｙ100Ｓ、Ｙ100Ｔ、Ｇ101Ａ、Ｈ102Ｗ、Ｅ103Ｆ、Ｅ103Ｈ、Ｅ103Ｎ、Ｅ103Ｑ、Ｅ103Ｒ、Ｅ103Ｖ、Ｅ103Ｗ、Ｖ104Ｄ、Ｖ104Ｅ、Ｖ104Ｆ、Ｖ104Ｈ、Ｖ104Ｋ、Ｖ104Ｌ、Ｖ104Ｒ、Ｇ105Ａ、Ｇ105Ｈ、Ｇ105Ｓ、Ｇ105Ｔ、Ｅ106Ｄ、Ｋ106Ｄ、Ｋ106Ｅ、Ｋ106Ｈ、Ｋ106Ｎ、Ｒ107Ｐ、Ｒ107Ｓ、Ｐ108Ｒ、Ｉ110Ａ、Ｉ110Ｆ、Ｉ110Ｌ、Ｉ110Ｍ、Ｉ110Ｔ、Ｔ111Ｄ、Ｔ111Ｈ、Ｔ111Ｎ、Ｔ111Ｒ、Ｇ112Ａ、Ｇ112Ｃ、Ｇ112Ｄ、Ｇ112Ｋ、Ｇ112Ｌ、Ｇ112Ｍ、Ｇ112Ｑ、Ｇ112Ｒ、Ｇ112Ｓ、Ｇ112Ｔ、Ｇ112Ｙ、Ｎ127Ｋ、Ｉ131Ｖ、Ａ132Ｖ、Ｌ133Ｖ、Ａ136Ｔ、Ｌ137Ｔ、Ｔ138Ｓ、Ｎ140Ｄ、Ｈ142Ｑ、Ｑ14Ｒ、Ｙ156Ｈ、Ｋ163Ｔ、Ｄ168Ｅ、Ｈ169Ｒ、Ｑ175Ｌ、Ｉ183Ｆ、Ｉ183Ｌ、Ｉ183Ｐ、Ｉ183Ｓ、Ｅ184Ａ、Ｅ184Ｄ、Ｅ184Ｒ、Ｅ184Ｔ、Ｅ184Ｖ、Ｅ185Ｔ、Ｍ187Ｌ、Ｍ189Ｉ、Ｋ191Ａ、Ｋ191Ｇ、Ｋ191Ｈ、Ｋ191Ｍ、Ｋ191Ｎ、Ｋ191Ｒ、Ｋ191Ｓ、Ｋ191Ｔ、Ｋ191Ｗ、Ｅ197Ａ、Ｅ197Ｄ、Ｅ197Ｆ、Ｅ197Ｋ、Ｅ197Ｍ、Ｅ197Ｑ、Ｅ197Ｓ、Ｅ197Ｔ、Ｅ197Ｖ、Ｉ201Ｃ、Ｉ201Ｅ、Ｉ201Ｆ、Ｉ201Ｈ、Ｉ201Ｌ、Ｉ201Ｓ、Ｉ201Ｔ、Ｉ201Ｖ、Ｈ203Ｋ、Ｌ219Ｍ、Ｌ219Ｗ、Ｆ220Ｌ、Ｖ223Ｉ、Ｆ225Ｙ、Ｈ230Ｆ、Ｈ230Ｌ、Ｈ230Ｙ、Ｎ232Ｓ、Ｙ246Ｆ、Ｆ249Ｗ、Ｄ250Ｅ、Ｓ274Ａ、Ｓ274Ｃ、Ｓ274Ｇ、Ｓ274Ｎ、Ｓ274Ｔ、Ｌ278Ｍ、Ａ280Ｇ、Ａ280Ｓ、Ａ280Ｔ、Ｇ281Ｓ、Ａ282Ｍ、Ａ282Ｐ、Ｇ284Ｎ、Ｉ285Ｌ、Ｖ303Ｌ、Ｖ303Ｓ、Ｆ306Ｗ、Ｆ306Ｙ、Ｓ311Ｎ、Ｋ315Ｅ、Ｄ317Ｅ、Ｄ317Ｋ、Ｉ331Ｃ、Ｉ331Ｌ、Ｉ331Ｎ、Ｉ331Ｓ、Ｉ331Ｔ、Ｉ331Ｖ、Ｎ333Ｔ、Ｐ334Ｎ、Ｐ335Ｔ、Ｌ337Ｔ、Ｌ338Ａ、Ｌ338Ｑ、Ｓ341Ｉ、Ｋ373Ｅ、Ｋ373Ｎ、Ｎ375Ａ、Ｎ375Ｈ、Ｙ376Ｃ、Ｙ376Ｆ、Ｙ376Ｌ、Ｋ378Ｇ、Ｋ378Ｐ、Ｋ378Ｑ、Ｋ378Ｒ、Ｋ380Ｇ、Ｋ380Ｓ、Ａ382Ｇ、Ａ382Ｒ、Ａ382Ｔ、Ｔ383Ｓ、Ｋ384Ｇ、Ｋ384Ｎ、Ｐ386Ｋ、Ｐ386Ｓ、Ｖ387Ｌ、Ｎ389Ｅ、Ｉ405Ｌ、Ｆ407Ｙ、Ｓ408Ｄ、Ｓ408Ｎ、Ｎ411Ｒ、Ｄ413Ｓ、Ｄ413Ｖ、Ｑ416Ｔ、Ｅ419Ａ、Ｅ419Ｌ、Ｋ420Ｅ、Ｒ421Ｎ、Ｖ424Ｉ、Ｋ427Ｍ、Ｎ429Ｅ、Ｇ432Ａ、及びＡ436Ｔからなる群から選択される少なくとも1つの置換を含む、前記修飾ヒトキヌレニナーゼ酵素。
[本発明1002]
前記アミノ酸配列が、表1のポリペプチドのうちのいずれか1つのアミノ酸配列に少なくとも90％同一である、本発明1001の酵素。
[本発明1003]
（ａ）Ａ282、Ｆ306、又はＦ249における置換；
（ｂ）Ｆ306Ｗ置換；
（ｃ）Ｌ72Ｎ置換；
（ｄ）Ｈ102Ｗ及びＮ333Ｔ置換；
（ｅ）Ａ99における置換；
（ｆ）Ｇ112における置換；
（ｇ）Ｅ103における置換；
（ｈ）Ｖ104における置換；
（ｉ）Ｓ408における置換；
（ｊ）Ｉ183Ｐ置換；
（ｋ）Ｒ107Ｐ置換；並びに／又は
（ｌ）Ａ436Ｔ置換
を含む、本発明1001の酵素。
[本発明1004]
Ｌ72Ｎ、Ｈ102Ｗ、Ａ282Ｐ、Ｆ306Ｗ、Ｉ331Ｓ、及びＮ333Ｔから選択される少なくとも1つの置換を含み、任意で、Ｌ72Ｎ、Ｈ102Ｗ、Ａ282Ｐ、Ｆ306Ｗ、Ｉ331Ｓ、及びＮ333Ｔから選択される少なくとも2つ、3つ、4つ、又は5つの置換を含む、本発明1001の酵素。
[本発明1005]
置換Ｌ72Ｎ、Ｈ102Ｗ、Ａ282Ｐ、Ｆ306Ｗ、Ｉ331Ｓ、及びＮ333Ｔを含む、本発明1004の酵素。
[本発明1006]
少なくとも8000Ｍ －1 ｓ －1 の、キヌレニン（ＫＹＮ）に対する触媒活性（ｋｃａｔ／ｋＭ）を有し、任意で、約8000Ｍ －1 ｓ －1 ～40000Ｍ －1 ｓ －1 ；10000Ｍ －1 ｓ －1 ～40000Ｍ －1 ｓ －1 ；20000Ｍ －1 ｓ －1 ～40000Ｍ －1 ｓ －1 ；又は25000Ｍ －1 ｓ －1 ～35000Ｍ －1 ｓ －1 の、ＫＹＮに対する触媒活性を有する、本発明1005の酵素。
[本発明1007]
前記アミノ酸配列が配列番号：2のアミノ酸配列に少なくとも90％同一であり、任意で、前記アミノ酸配列が配列番号：2のアミノ酸配列に少なくとも95％同一である、本発明1001の酵素。
[本発明1008]
異種ペプチドセグメントを更に含む、本発明1001～1007のいずれかの酵素。
[本発明1009]
ポリエチレングリコール（ＰＥＧ）と結合しており、任意で、1つ以上のＬｙｓ又はＣｙｓ残基にてＰＥＧと結合している、本発明1001～1007のいずれかの酵素。
[本発明1010]
本発明1001～1008のいずれかの酵素をコードするヌクレオチド配列を含む核酸であって、任意で、細菌、菌類、昆虫、又は哺乳類での発現のためにコドン最適化されている、前記核酸。
[本発明1011]
本発明1010の核酸を含む発現ベクター。
[本発明1012]
本発明1010の核酸又は本発明1011の発現ベクターを含む宿主細胞であって、任意で、前記宿主細胞が細菌細胞、真菌細胞、昆虫細胞、又は哺乳類細胞であり、任意で、前記哺乳類細胞が哺乳類免疫エフェクター細胞であり、任意で、前記哺乳類免疫エフェクター細胞がＮＫ細胞又はＴ細胞である、前記宿主細胞。
[本発明1013]
薬学上許容される担体の中に本発明1001～1009のいずれかの酵素を含む、医薬製剤。
[本発明1014]
腫瘍を有する対象に、有効量の、本発明1001～1009のいずれかの酵素又は本発明1013の製剤を投与することを含む、腫瘍を有する対象の治療方法。
[本発明1015]
腫瘍を有する対象の治療に使用するための、有効量の、本発明1001～1009のいずれかの酵素又は本発明1013の製剤を含む、組成物。
[本発明1016]
前記対象が、ＩＤＯ1、ＩＤＯ2、又はＴＤＯを発現する腫瘍を有するものとして同定されており、任意で、
（ａ）前記腫瘍が充実性腫瘍又は血液腫瘍であり；
（ｂ）前記対象がヒト患者であり；
（ｃ）前記酵素又は製剤が、腫瘍内に、静脈内に、皮内に、動脈内に、腹腔内に、病巣内に、頭蓋内に、関節内に、前立腺内に、胸膜内に、気管内に、眼内に、鼻孔内に、硝子体内に、腟内に、直腸内に、筋肉内に、皮下に、結膜下に、膀胱内に、粘膜に、心膜内に、臍帯内に、経口で、吸入により、注射により、注入により、連続注入により、標的細胞を直接浸す局所潅流により、カテーテルを介して、又は洗浄により投与され；かつ／又は
（ｄ）前記酵素又は製剤が、少なくとも第2の抗癌治療法と共に投与され、任意で、前記第2の抗癌治療法が放射線治療、外科治療、免疫療法、又は第2の抗癌性化合物であり、任意で、
（ｉ）前記第2の抗癌性化合物が免疫チェックポイント阻害剤であり、任意で、前記免疫チェックポイント阻害剤が抗体又は抗体薬物コンジュゲートであり、任意で、前記抗体が抗ＰＤ1抗体、抗ＣＴＬＡ－4抗体、又は抗ＰＤ－Ｌ1抗体であり；かつ／又は
（ｉｉ）前記免疫療法が、免疫エフェクター細胞又は免疫原性組成物を投与することを含み、任意で、前記免疫原性組成物が癌細胞抗原を含み、かつ／又は前記免疫エフェクター細胞がＮＫ細胞、Ｔ細胞、又はＣＡＲ Ｔ細胞を含む、
本発明1014の方法又は本発明1015の組成物。
[本発明1017]
本発明1001～1008のいずれかの発現されたキヌレニナーゼ酵素を含む、トランスジェニックＴ細胞であって、任意で、
（ａ）前記トランスジェニックＴ細胞が、発現されたキメラ抗原Ｔ細胞受容体（ＣＡＲ）又は組換えされたＴ細胞受容体（ＴＣＲ）を更に含み；
（ｂ）前記トランスジェニックＴ細胞がヒトトランスジェニックＴ細胞であり；
（ｃ）前記ＣＡＲ及び前記キヌレニナーゼをコードするＤＮＡが、前記細胞のゲノムに組み込まれており；かつ／又は
（ｄ）前記ＣＡＲが癌細胞抗原に対して標的化され、任意で、前記癌細胞抗原がＨＥＲ2、ＣＤ19、ＣＤ20、又はＧＤ2である、
前記トランスジェニックＴ細胞。
[本発明1018]
腫瘍を有するヒト対象に、有効量の本発明1017のトランスジェニック細胞を投与することを含む、腫瘍を有するヒト対象におけるＴ細胞応答を促進する方法。
[本発明1019]
腫瘍を有する対象の治療で使用するための、有効量の本発明1017のトランスジェニック細胞を含む組成物であって、任意で、
（ａ）前記トランスジェニック細胞が自己由来である；又は
（ｂ）前記トランスジェニック細胞が異種由来である、
前記組成物。
[本発明1020]
腫瘍の治療のための薬剤の製造における、本発明1001～1009のいずれかのキヌレニナーゼ酵素又は本発明1010の核酸の使用。
本発明の他の目的、特徴及び利点は、以下の詳細な説明から明らかになるだろう。しかし、詳細な説明及び具体例は、本発明の特定実施形態を示しているが、単なる具体例として与えられていることが理解されるべきである。本発明の精神及び範囲内の種々の変更及び改変が、この詳細な説明から当業者には明らかになるからである。
[Invention 1001]
An isolated modified human quinureninase enzyme having an amino acid sequence that is at least 90% identical to the human quinureninase enzyme of SEQ ID NO: 1 and L8P, K38E, Y47L, I48F, K50Q, I51M, S60N, K64N, D65G, E66K, N67D, N67P, D67S, A68F, A68T, A68V, F71L, F71M, L72N, K84E, E88N, E89K, E89S, E90Q, D92E, K93N, K93T, A95H, A95Q, K96 I97L, I97V, A98G, A99G, A99I, A99R, A99S, A99T, A99V, Y100N, Y100S, Y100T, G101A, H102W, E103F, E103H, E103N, E103Q, E103R, E103V, E103W, V104D, V104E, V104F V104K, V104L, V104R, G105A, G105H, G105S, G105T, E106D, K106D, K106E, K106H, K106N, R107P, R107S, P108R, I110A, I110F, I110L, I110M, I110T, T111D, T111H, T111N, T111R G112C, G112D, G112K, G112L, G112M, G112Q, G112R, G112S, G112T, G112Y, N127K, I131V, A132V, L133V, A136T, L137T, T138S, N140D, H142Q, Q14R, Y156H, K163T, D168E, H169R I183F, I183L, I183P, I183S, E184A, E184D, E184R, E184T, E184V, E185T, M187L, M189I, K191A, K191G, K191H, K191M, K191N, K191R, K191S, K191T, K191W, E197A, E197D, E197F E197M, E197Q, E197S, E197T, E197V, I201C, I201E, I201F, I201H, I201L, I201S, I201T, I201V, H203K, L219M, L219W, F220L, V223I, F225Y, H230F, H230L, H230Y, N232S, Y246F D250E, S274A, S274C, S274G, S274N, S274T, L27 8M, A280G, A280S, A280T, G281S, A282M, A282P, G284N, I285L, V303L, V303S, F306W, F306Y, S311N, K315E, D317E, D317K, I331C, I331L, I331N, I331S, I331T, I331V, N333T P335T, L337T, L338A, L338Q, S341I, K373E, K373N, N375A, N375H, Y376C, Y376F, Y376L, K378G, K378P, K378Q, K378R, K380G, K380S, A382G, A382R, A382T, T383S, K384G, K384N At least one selected from the group consisting of P386S, V387L, N389E, I405L, F407Y, S408D, S408N, N411R, D413S, D413V, Q416T, E419A, E419L, K420E, R421N, V424I, K427M, N429E, G432A, and A436T. The modified human quinureninase enzyme comprising a substitution.
[Invention 1002]
The enzyme of the invention 1001 whose amino acid sequence is at least 90% identical to the amino acid sequence of any one of the polypeptides in Table 1.
[Invention 1003]
(A) Substitution in A282, F306, or F249;
(B) F306W substitution;
(C) L72N substitution;
(D) H102W and N333T substitution;
(E) Substitution in A99;
(F) Substitution in G112;
(G) Substitution in E103;
(H) Substitution in V104;
(I) Substitution in S408;
(J) I183P substitution;
(K) R107P substitution; and / or
(L) A436T substitution
The enzyme of the present invention 1001 including.
[Invention 1004]
Containing at least one substitution selected from L72N, H102W, A282P, F306W, I331S, and N333T and optionally at least two, three, four selected from L72N, H102W, A282P, F306W, I331S, and N333T. The enzyme of the invention 1001 comprising one or five substitutions.
[Invention 1005]
The enzyme of the invention 1004 comprising substituted L72N, H102W, A282P, F306W, I331S, and N333T.
[Invention 1006]
It has at least 8000M -1 s -1 catalytic activity (kcat / km) for kynurenine (KYN) and is optionally about 8000M -1 s -1 to 40000M -1 s -1 ; 10000M- 1 s - 1 to. The enzyme of the present invention 1005 having catalytic activity for KYN of 40000M - 1 s -1 ; 20000M -1 s -1 to 40000M -1 s -1 ; or 25000M -1 s -1 to 35000M -1 s -1 .
[Invention 1007]
The enzyme of the invention 1001 wherein the amino acid sequence is at least 90% identical to the amino acid sequence of SEQ ID NO: 2, and optionally, the amino acid sequence is at least 95% identical to the amino acid sequence of SEQ ID NO: 2.
[Invention 1008]
The enzyme of any of 1001-1007 of the present invention, further comprising a heterologous peptide segment.
[Invention 1009]
The enzyme of any of 1001-1007 of the invention, which is bound to polyethylene glycol (PEG) and optionally to PEG at one or more Lys or Cys residues.
[Invention 1010]
A nucleic acid comprising a nucleotide sequence encoding any of the enzymes 1001-1008 of the present invention, optionally codon-optimized for expression in a bacterium, fungus, insect, or mammal.
[Invention 1011]
An expression vector containing the nucleic acid of the present invention 1010.
[Invention 1012]
A host cell comprising the nucleic acid of the invention 1010 or the expression vector of the invention 1011, optionally said the host cell is a bacterial cell, a fungal cell, an insect cell, or a mammalian cell, and optionally the mammalian cell is a mammal. The host cell, which is an immune effector cell and optionally the mammalian immune effector cell is an NK cell or a T cell.
[Invention 1013]
A pharmaceutical preparation containing any of the enzymes 1001 to 1009 of the present invention in a pharmaceutically acceptable carrier.
[Invention 1014]
A method for treating a subject having a tumor, which comprises administering an effective amount of an enzyme according to any one of 1001 to 1009 of the present invention or a preparation of the present invention 1013 to the subject having the tumor.
[Invention 1015]
A composition comprising an effective amount of an enzyme according to any one of 1001 to 1009 of the present invention or a preparation of 1013 of the present invention for use in the treatment of a subject having a tumor.
[Invention 1016]
The subject has been identified as having a tumor expressing IDO1, IDO2, or TDO, and optionally.
(A) The tumor is a solid tumor or a hematological tumor;
(B) The subject is a human patient;
(C) The enzyme or preparation can be used in tumors, veins, skin, arteries, abdomen, lesions, skulls, joints, prostates, thoracic membranes, and qi. Intravital, intravitreal, intravitreal, intravitreal, vaginal, rectal, intramuscular, subcutaneous, subconjunctival, bladder, mucosal, pericardial, umbilical cord, Administered orally, by inhalation, by injection, by infusion, by continuous infusion, by local perfusion directly immersing the target cells, via a catheter, or by lavage; and / or
(D) The enzyme or formulation is administered with at least a second anti-cancer treatment, optionally the second anti-cancer treatment is radiation therapy, surgical treatment, immunotherapy, or a second anti-cancer compound. And optional,
(I) The second anti-cancer compound is an immune checkpoint inhibitor, optionally the immune checkpoint inhibitor is an antibody or antibody drug conjugate, and optionally the antibody is an anti-PD1 antibody, anti-PD1 antibody. CTLA-4 antibody, or anti-PD-L1 antibody; and / or
(Ii) The immunotherapy comprises administering an immunogenic effector cell or an immunogenic composition, optionally the immunogenic composition comprises a cancer cell antigen and / or the immunogenic effect cell is an NK cell. , T cells, or CAR T cells,
The method of the present invention 1014 or the composition of the present invention 1015.
[Invention 1017]
A transgenic T cell comprising the expressed kynureninase enzyme of any of 1001 to 1008 of the present invention, optionally.
(A) The transgenic T cell further comprises an expressed chimeric antigen T cell receptor (CAR) or recombinant T cell receptor (TCR);
(B) The transgenic T cells are human transgenic T cells;
(C) The DNA encoding the CAR and the kynureninase are integrated into the genome of the cell; and / or
(D) The CAR is targeted against a cancer cell antigen, and optionally the cancer cell antigen is HER2, CD19, CD20, or GD2.
The transgenic T cells.
[Invention 1018]
A method of promoting a T cell response in a human subject with a tumor, comprising administering to the human subject with the tumor an effective amount of transgenic cells of the invention 1017.
[Invention 1019]
A composition comprising an effective amount of transgenic cells of the invention 1017 for use in the treatment of a subject having a tumor, optionally.
(A) The transgenic cells are self-derived; or
(B) The transgenic cells are of heterogeneous origin.
The composition.
[Invention 1020]
Use of the kynureninase enzyme of the present invention 1001 to 1009 or the nucleic acid of the present invention 1010 in the manufacture of a drug for the treatment of a tumor.
Other objects, features and advantages of the invention will become apparent from the detailed description below. However, although the detailed description and specific examples show specific embodiments of the present invention, it should be understood that they are given as mere specific examples. This detailed description reveals to those skilled in the art various changes and modifications within the spirit and scope of the invention.
Claims (30)
（ｂ）前記対象がヒト患者であり；(B) The subject is a human patient;
（ｃ）前記組成物が、腫瘍内、静脈内、皮内、動脈内、腹腔内、病巣内、頭蓋内、関節内、前立腺内、胸膜内、気管内、眼内、鼻孔内、硝子体内、腟内、直腸内、筋肉内、皮下、結膜下、膀胱内、粘膜、心膜内、臍帯内、経口、吸入による、注射による、注入による、連続注入による、標的細胞を直接浸す局所潅流による、カテーテルを介する、又は洗浄による投与のために製剤化され；かつ／又は(C) The composition comprises intratumor, intravenous, intracutaneous, intraarterial, intraperitoneal, intralesional, intracranial, intra-arterial, intraprostatic, intrathoracic, intratracheal, intraocular, intranasal, intragranular. Intravaginal, rectal, intramuscular, subcutaneous, subconjunctival, intravesical, mucosal, intrathecal, intraumbilical, oral, by inhalation, by injection, by infusion, by continuous infusion, by local perfusion directly immersing the target cells, Formulated for administration via catheter or by lavage; and / or
（ｄ）前記組成物が、少なくとも第２の抗癌治療法と共に投与するために製剤化されている、(D) The composition is formulated for administration with at least a second anti-cancer treatment.
請求項１６に記載の組成物。The composition according to claim 16.
（ｉｉ）前記免疫療法が、免疫エフェクター細胞又は免疫原性組成物を投与することを含む、(Ii) The immunotherapy comprises administering an immunoeffector cell or an immunogenic composition.
請求項１９に記載の組成物。The composition according to claim 19.
（ｂ）前記トランスジェニックＴ細胞がヒトトランスジェニックＴ細胞であり；(B) The transgenic T cells are human transgenic T cells;
（ｃ）前記ＣＡＲ及び前記キヌレニナーゼをコードするＤＮＡが、前記細胞のゲノムに組み込まれており；かつ／又は(C) The DNA encoding the CAR and the kynureninase are integrated into the genome of the cell; and / or
（ｄ）前記ＣＡＲが癌細胞抗原に対して標的化される、(D) The CAR is targeted against a cancer cell antigen.
請求項２４に記載のトランスジェニックＴ細胞。The transgenic T cell according to claim 24.
（ｂ）前記トランスジェニック細胞が異種由来である、(B) The transgenic cells are of heterogeneous origin.
請求項２７に記載の組成物。27. The composition of claim 27.
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| US62/658,261 | 2018-04-16 | ||
| PCT/US2019/027623 WO2019204269A1 (en) | 2018-04-16 | 2019-04-16 | Human kynureninase enzymes and uses thereof |
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| JP2021521777A JP2021521777A (en) | 2021-08-30 |
| JPWO2019204269A5 true JPWO2019204269A5 (en) | 2022-04-07 |
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| EP3423483A4 (en) | 2016-03-02 | 2019-08-21 | Board Of Regents Of the University Of Texas System | Human kynureninase enzyme variants having improved pharmacological properties |
| WO2024085280A1 (en) * | 2022-10-20 | 2024-04-25 | 서울대학교 산학협력단 | Novel kynureninase and use thereof |
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| AU2003212850A1 (en) | 2002-02-01 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Methods and compositions for treating cardiovascular disease |
| CN1330774C (en) | 2002-03-01 | 2007-08-08 | 国家人类基因组南方研究中心 | Kynurenine hydrolase polymorphism and its diagnostic use |
| EP1613308A4 (en) | 2003-03-27 | 2008-02-20 | Lankenau Inst Medical Res | Novel methods for the treatment of cancer |
| US20070207158A1 (en) | 2003-06-17 | 2007-09-06 | Harrison Roger G | Conjugate for the specific targeting of anticancer agents to tumor cells or tumor vasculature and production thereof |
| JP4733635B2 (en) | 2003-07-31 | 2011-07-27 | イミューノメディクス、インコーポレイテッド | Anti-CD19 antibody |
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| ES2444574T3 (en) | 2006-09-19 | 2014-02-25 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indolamine 2,3-dioxygenase |
| WO2011041093A1 (en) | 2009-10-01 | 2011-04-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-vascular endothelial growth factor receptor-2 chimeric antigen receptors and use of same for the treatment of cancer |
| US9212229B2 (en) | 2010-09-08 | 2015-12-15 | Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus | Chimeric antigen receptors with an optimized hinge region |
| MX347078B (en) | 2010-12-09 | 2017-04-10 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer. |
| WO2012099441A2 (en) | 2011-01-21 | 2012-07-26 | 인제대학교산학협력단 | Immune response inhibiting composition containing stem cells expressing tryptophan metabolizing enzyme genes |
| KR20120085209A (en) | 2011-01-21 | 2012-07-31 | 인제대학교 산학협력단 | Composition for inhibiting immune response comprising stem cell expressing tryptophan metabolic enzyme gene |
| RU2640913C2 (en) | 2011-09-07 | 2018-01-12 | Дойчес Кребсфоршунгсцентрум | Means and methods for cancer treatment and/or prevention depending on natural ahr ligand |
| ES2654060T3 (en) | 2011-10-20 | 2018-02-12 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Anti-CD22 chimeric antigen receptors |
| CN113957061A (en) | 2013-08-30 | 2022-01-21 | 得克萨斯大学体系董事会 | Administration of kynurenine depleting enzymes for tumor therapy |
| IL250833B (en) | 2014-08-29 | 2022-09-01 | Univ Texas | Administration of kynurenine depleting enzymes for tumor therapy |
| EP3423483A4 (en) * | 2016-03-02 | 2019-08-21 | Board Of Regents Of the University Of Texas System | Human kynureninase enzyme variants having improved pharmacological properties |
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